Haplogroup E-V68 , also known as E1b1b1a , is a major human Y-chromosome DNA haplogroup found in North Africa , the Horn of Africa , Western Asia and Europe . It is a subclade of the larger and older haplogroup, known as E1b1b or E-M215 (also roughly equivalent to E-M35). The E1b1b1a lineage is identified by the presence of a single nucleotide polymorphism (SNP) mutation on the Y chromosome , which is known as V68. It is a subject of discussion and study in genetics as well as genetic genealogy , archaeology , and historical linguistics .
106-560: E-V68 is dominated by its longer-known subclade E-M78 . In various publications, both E-V68 and E-M78 have been referred to by other names, especially phylogenetic nomenclature such as "E3b1a" which are designed to show their place on the family tree of all males. These various names change as new discoveries are made and are discussed below. E-M78, like its parent clade E-V68, is thought to have an African origin. Based on genetic STR variance data, Cruciani et al. (2007) suggests that this subclade originated in "Northeastern Africa", which in
212-699: A GAA triplet expansion in the first intron of the X25 gene appears to interfere with transcription, and causes Friedreich's ataxia . Tandem repeats in the first intron of the Asparagine synthetase gene are linked to acute lymphoblastic leukaemia. A repeat polymorphism in the fourth intron of the NOS3 gene is linked to hypertension in a Tunisian population. Reduced repeat lengths in the EGFR gene are linked with osteosarcomas. An archaic form of splicing preserved in zebrafish
318-460: A SNP-defined linkage disequilibrium block of interest. Thus, microsatellites have successfully led to discoveries of type 2 diabetes ( TCF7L2 ) and prostate cancer genes (the 8q21 region). Microsatellites were popularized in population genetics during the 1990s because as PCR became ubiquitous in laboratories researchers were able to design primers and amplify sets of microsatellites at low cost. Their uses are wide-ranging. A microsatellite with
424-1023: A Spanish funeral cave dated to approximately 7000 years ago were in the E-V13 branch of E-M78. In June 2015, the M78 mutation and the consequent beginning of the E-M78 and E-V68 family trees was dated by Trombetta et al. to approximately 20,300-14,800 years ago. This phylogenetic tree of haplogroup subclades is based on the ISOGG 2019 tree, as well as the FamilyTreeDNA™ tree. E-V68* (E1b1b1a*) E-M78* (E1b1b1a1*) (Gurna Oasis) in Egypt, Morocco and Mediterranean. E-V12* (E1b1b1a1a*) Found in Egypt, French Basques, Sudan, and other places. E-BY8673 Found in Arabian Peninsula E-BY8350 Found in
530-613: A Spanish funeral cave dated to approximately 7000 years ago were in the E-V13 branch of E-M78. In June 2015, the M78 mutation and the consequent beginning of the E-M78 and E-V68 family trees was dated by Trombetta et al. to approximately 20,300-14,800 years ago. This phylogenetic tree of haplogroup subclades is based on the ISOGG 2019 tree, as well as the FamilyTreeDNA™ tree. E-V68* (E1b1b1a*) E-M78* (E1b1b1a1*) (Gurna Oasis) in Egypt, Morocco and Mediterranean. E-V12* (E1b1b1a1a*) Found in Egypt, French Basques, Sudan, and other places. E-BY8673 Found in Arabian Peninsula E-BY8350 Found in
636-455: A conserved or nonconserved region, this technique is not useful for distinguishing individuals, but rather for phylogeography analyses or maybe delimiting species ; sequence diversity is lower than in SSR-PCR, but still higher than in actual gene sequences. In addition, microsatellite sequencing and ISSR sequencing are mutually assisting, as one produces primers for the other. Repetitive DNA
742-637: A decline in frequency going west to east in the Levantine-Syria region. Keita identified high frequencies of M35 (>50%) among Omotic populations, but stated that this derived from a small, published sample of 12. Keita also wrote that the PN2 mutation was shared by M35 and M2 lineages and this defined clade originated from East Africa. He concluded that "the genetic data give population profiles that clearly indicate males of African origin, as opposed to being of Asian or European descent" but acknowledged that
848-515: A genome region between microsatellite loci. The complementary sequences to two neighboring microsatellites are used as PCR primers; the variable region between them gets amplified. The limited length of amplification cycles during PCR prevents excessive replication of overly long contiguous DNA sequences, so the result will be a mix of a variety of amplified DNA strands which are generally short but vary much in length. Sequences amplified by ISSR-PCR can be used for DNA fingerprinting. Since an ISSR may be
954-520: A given trait or disease. Microsatellites are also used in population genetics to measure levels of relatedness between subspecies, groups and individuals. Although the first microsatellite was characterised in 1984 at the University of Leicester by Weller, Jeffreys and colleagues as a polymorphic GGAT repeat in the human myoglobin gene, the term "microsatellite" was introduced later, in 1989, by Litt and Luty. The name "satellite" DNA refers to
1060-761: A high degree of error-free data while being short enough to survive degradation in non-ideal conditions. Even shorter repeat sequences would tend to suffer from artifacts such as PCR stutter and preferential amplification, while longer repeat sequences would suffer more highly from environmental degradation and would amplify less well by PCR . Another forensic consideration is that the person's medical privacy must be respected, so that forensic STRs are chosen which are non-coding, do not influence gene regulation, and are not usually trinucleotide STRs which could be involved in triplet expansion diseases such as Huntington's disease . Forensic STR profiles are stored in DNA databanks such as
1166-457: A higher mutation rate than other areas of DNA leading to high genetic diversity . Microsatellites are often referred to as short tandem repeats ( STRs ) by forensic geneticists and in genetic genealogy , or as simple sequence repeats ( SSRs ) by plant geneticists. Microsatellites and their longer cousins, the minisatellites , together are classified as VNTR (variable number of tandem repeats ) DNA. The name "satellite" DNA refers to
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#17327811942671272-497: A microsatellite repeat, if present on the DNA segment. If positive clones can be obtained from this procedure, the DNA is sequenced and PCR primers are chosen from sequences flanking such regions to determine a specific locus . This process involves significant trial and error on the part of researchers, as microsatellite repeat sequences must be predicted and primers that are randomly isolated may not display significant polymorphism. Microsatellite loci are widely distributed throughout
1378-515: A minor subclade. Its discovery was announced in Underhill et al. (2001) and Shen et al. (2004) found 1 out of their 20 Yemeni Israelis they tested. Cruciani et al. (2006) called M224 "rare and rather uninformative" and they found no exemplars. Cruciani et al. (2007) suggest that this subclade of E-V12 originated in North Africa , and then subsequently expanded further south into
1484-399: A minor subclade. Its discovery was announced in Underhill et al. (2001) and Shen et al. (2004) found 1 out of their 20 Yemeni Israelis they tested. Cruciani et al. (2006) called M224 "rare and rather uninformative" and they found no exemplars. Cruciani et al. (2007) suggest that this subclade of E-V12 originated in North Africa , and then subsequently expanded further south into
1590-403: A neutral evolutionary history makes it applicable for measuring or inferring bottlenecks , local adaptation , the allelic fixation index (F ST ), population size , and gene flow . As next generation sequencing becomes more affordable the use of microsatellites has decreased, however they remain a crucial tool in the field. Marker assisted selection or marker aided selection (MAS)
1696-1105: A new central African lineage defined by V259. The rare M78 subhaplogroup E1b1b1a1-PF2186 has been found at highest frequencies among the Toubou population inhabiting Chad (21%). This subclade of E-M78 is the one which appears to have split from the others first (it arose c. 13.7-15.2 kya ). According to Cruciani et al. (2007) , the E-V12 sublineage likely originated in North Africa . Undifferentiated E-V12* lineages (not E-V32 or E-M224, so therefore named "E-V12*") peak in frequency among Southern Egyptians (up to 74.5%). The subclades are also scattered widely in small amounts in both Northern Africa and Europe, but with very little sign in Western Asia, apart from Turkey. These E-V12* lineages were formerly included (along with many E-V22* lineages ) in Cruciani et al.'s original (2004) "delta cluster", which he had defined using Y-STR profiles. With
1802-878: A new central African lineage defined by V259. The rare M78 subhaplogroup E1b1b1a1-PF2186 has been found at highest frequencies among the Toubou population inhabiting Chad (21%). This subclade of E-M78 is the one which appears to have split from the others first (it arose c. 13.7-15.2 kya). According to Cruciani et al. (2007) , the E-V12 sublineage likely originated in North Africa . Undifferentiated E-V12* lineages (not E-V32 or E-M224, so therefore named "E-V12*") peak in frequency among Southern Egyptians (up to 74.5%). The subclades are also scattered widely in small amounts in both Northern Africa and Europe, but with very little sign in Western Asia, apart from Turkey. These E-V12* lineages were formerly included (along with many E-V22* lineages) in Cruciani et al.'s original (2004) "delta cluster", which he had defined using Y-STR profiles. With
1908-480: A point mutation has created an extended GGAA microsatellite which binds a transcription factor, which in turn activates the EGR2 gene which drives the cancer. In addition, other GGAA microsatellites may influence the expression of genes that contribute to the clinical outcome of Ewing sarcoma patients. Microsatellites within introns also influence phenotype, through means that are not currently understood. For example,
2014-408: A recent bottleneck in the population or a proximity to the origin of the haplogroup." However, More recently, Tillmar et al. (2009) typed 147 males from Somalia for 12 Y-STR loci, and observed that 77% (113/147) had typical E-V32 haplotypes. This is the highest frequency of E-V32 found in any single sample population. Haplogroup E-M78 (Y-DNA) Haplogroup E-V68 , also known as E1b1b1a ,
2120-664: A recent bottleneck in the population or a proximity to the origin of the haplogroup." However, More recently, Tillmar et al. (2009) typed 147 males from Somalia for 12 Y-STR loci, and observed that 77% (113/147) had typical E-V32 haplotypes. This is the highest frequency of E-V32 found in any single sample population. Microsatellite A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs ) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome . They have
2226-399: A single nucleotide, microsatellite mutations lead to the gain or loss of an entire repeat unit, and sometimes two or more repeats simultaneously. Thus, the mutation rate at microsatellite loci is expected to differ from other mutation rates, such as base substitution rates. The mutation rate at microsatellite loci depends on the repeat motif sequence, the number of repeated motif units and
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#17327811942672332-489: A source of genetic predisposition in a variety of cancers. Microsatellite analysis became popular in the field of forensics in the 1990s. It is used for the genetic fingerprinting of individuals where it permits forensic identification (typically matching a crime stain to a victim or perpetrator). It is also used to follow up bone marrow transplant patients. The microsatellites in use today for forensic analysis are all tetra- or penta-nucleotide repeats, as these give
2438-401: A tumour cell line might show a different genetic fingerprint from that of the host tissue, and, especially in colorectal cancer , might present with loss of heterozygosity . Microsatellites analyzed in primary tissue therefore been routinely used in cancer diagnosis to assess tumour progression. Genome Wide Association Studies (GWAS) have been used to identify microsatellite biomarkers as
2544-550: Is a large size difference between individual alleles, then there may be increased instability during recombination at meiosis. Another possible cause of microsatellite mutations are point mutations, where only one nucleotide is incorrectly copied during replication. A study comparing human and primate genomes found that most changes in repeat number in short microsatellites appear due to point mutations rather than slippage. Direct estimates of microsatellite mutation rates have been made in numerous organisms, from insects to humans. In
2650-580: Is a major human Y-chromosome DNA haplogroup found in North Africa , the Horn of Africa , Western Asia and Europe . It is a subclade of the larger and older haplogroup, known as E1b1b or E-M215 (also roughly equivalent to E-M35). The E1b1b1a lineage is identified by the presence of a single nucleotide polymorphism (SNP) mutation on the Y chromosome , which is known as V68. It is a subject of discussion and study in genetics as well as genetic genealogy , archaeology , and historical linguistics . E-V68
2756-574: Is an indirect selection process where a trait of interest is selected based on a marker ( morphological , biochemical or DNA / RNA variation) linked to a trait of interest (e.g. productivity, disease resistance, stress tolerance, and quality), rather than on the trait itself. Microsatellites have been proposed to be used as such markers to assist plant breeding. Repetitive DNA is not easily analysed by next generation DNA sequencing methods, for some technologies struggle with homopolymeric tracts. A variety of software approaches have been created for
2862-599: Is currently the highest frequency of E-V32 found in any single sample population. Similarly, Hassan et al. (2008) in their study observed this to be the most common of the sub-clades of E-M78 found in Sudan , especially among the Beja , Masalit and Fur . The Beja, like Somalis and Oromos, speak an Afro-Asiatic language and live along the "corridor" from the Horn of Africa to Egypt. Hassan et al. (2008) interpret this as reinforcing
2968-447: Is currently the highest frequency of E-V32 found in any single sample population. Similarly, Hassan et al. (2008) in their study observed this to be the most common of the sub-clades of E-M78 found in Sudan , especially among the Beja , Masalit and Fur . The Beja, like Somalis and Oromos, speak an Afro-Asiatic language and live along the "corridor" from the Horn of Africa to Egypt. Hassan et al. (2008) interpret this as reinforcing
3074-595: Is dominated by its E-V13 subclade, except in Iberia. E-V13 has a frequency peak centered in parts of the Balkans (approximately 20% in southern areas; up to almost 50% is some particular places and populations ) and Italy. It today has lower frequencies toward the western, central and northeastern areas, though E-V13 has been found in a Neolithic burial in Catalonia. This is discussed in more detail below. Listed here are
3180-429: Is dominated by its E-V13 subclade, except in Iberia. E-V13 has a frequency peak centered in parts of the Balkans (approximately 20% in southern areas; up to almost 50% is some particular places and populations) and Italy. It today has lower frequencies toward the western, central and northeastern areas, though E-V13 has been found in a Neolithic burial in Catalonia. This is discussed in more detail below. Listed here are
3286-554: Is dominated by its longer-known subclade E-M78 . In various publications, both E-V68 and E-M78 have been referred to by other names, especially phylogenetic nomenclature such as "E3b1a" which are designed to show their place on the family tree of all males. These various names change as new discoveries are made and are discussed below. E-M78, like its parent clade E-V68, is thought to have an African origin. Based on genetic STR variance data, Cruciani et al. (2007) suggests that this subclade originated in "Northeastern Africa", which in
Haplogroup E-V68 - Misplaced Pages Continue
3392-470: Is in turn the basis of the phylogeny given below. Keita (2008) examined a published Y-chromosome dataset on Afro-Asiatic populations and found that a key lineage E-M35 / E-M78 , sub-clade mutation of haplogroup E, was shared between the populations in the locale of original Egyptian speakers and modern Cushitic speakers from the Horn. These lineages are present in Egyptians, Berbers, Cushitic speakers from
3498-415: Is known to use microsatellite sequences within intronic mRNA for the removal of introns in the absence of U2AF2 and other splicing machinery. It is theorized that these sequences form highly stable cloverleaf configurations that bring the 3' and 5' intron splice sites into close proximity, effectively replacing the spliceosome . This method of RNA splicing is believed to have diverged from human evolution at
3604-417: Is repeatedly denatured at a high temperature to separate the double strand, then cooled to allow annealing of primers and the extension of nucleotide sequences through the microsatellite. This process results in production of enough DNA to be visible on agarose or polyacrylamide gels; only small amounts of DNA are needed for amplification because in this way thermocycling creates an exponential increase in
3710-443: Is the cause of microsatellite mutations. Typically, slippage in each microsatellite occurs about once per 1,000 generations. Thus, slippage changes in repetitive DNA are three orders of magnitude more common than point mutations in other parts of the genome. Most slippage results in a change of just one repeat unit, and slippage rates vary for different allele lengths and repeat unit sizes, and within different species. If there
3816-621: The Gurna Oasis (5.88%), with lower frequencies also observed in Moroccan Arabs , Sardinians and the Balkans . The highest frequencies of all the defined E-M78 sub-clades is primarily found amongst Afroasiatic -speaking populations in the large area stretching from the haplogroup's putative place of origin in Upper Egypt to the Sudan and the Horn of Africa . Outside of this core area of distribution (North Africa and
3922-436: The Gurna Oasis (5.88%), with lower frequencies also observed in Moroccan Arabs , Sardinians and the Balkans . The highest frequencies of all the defined E-M78 sub-clades is primarily found amongst Afroasiatic -speaking populations in the large area stretching from the haplogroup's putative place of origin in Upper Egypt to the Sudan and the Horn of Africa . Outside of this core area of distribution (North Africa and
4028-605: The HOXA13 gene are linked to hand-foot-genital syndrome , a developmental disorder in humans. Length changes in other triplet repeats are linked to more than 40 neurological diseases in humans, notably trinucleotide repeat disorders such as fragile X syndrome and Huntington's disease . Evolutionary changes from replication slippage also occur in simpler organisms. For example, microsatellite length changes are common within surface membrane proteins in yeast, providing rapid evolution in cell properties. Specifically, length changes in
4134-582: The Horn of Africa , where it is now prevalent. Before the discovery of V32, Cruciani et al. (2004) referred to the same lineages as the "gamma cluster", which was estimated to have arisen about 8,500 years ago. They stated that "the highest frequencies in the three Cushitic -speaking groups: the Borana from Kenya (71.4%), the Oromo from Ethiopia (32.0%), and the Somali (52.2%). Outside of eastern Africa, it
4240-426: The Horn of Africa , where it is now prevalent. Before the discovery of V32, Cruciani et al. (2004) referred to the same lineages as the "gamma cluster", which was estimated to have arisen about 8,500 years ago. They stated that "the highest frequencies in the three Cushitic -speaking groups: the Borana from Kenya (71.4%), the Oromo from Ethiopia (32.0%), and the Somali (52.2%). Outside of eastern Africa, it
4346-623: The UK National DNA Database (NDNAD), the American CODIS or the Australian NCIDD. Autosomal microsatellites are widely used for DNA profiling in kinship analysis (most commonly in paternity testing). Paternally inherited Y-STRs (microsatellites on the Y chromosome ) are often used in genealogical DNA testing . During the 1990s and the first several years of this millennium, microsatellites were
Haplogroup E-V68 - Misplaced Pages Continue
4452-547: The desert locust Schistocerca gregaria , the microsatellite mutation rate was estimated at 2.1 × 10 per generation per locus. The microsatellite mutation rate in human male germ lines is five to six times higher than in female germ lines and ranges from 0 to 7 × 10 per locus per gamete per generation. In the nematode Pristionchus pacificus , the estimated microsatellite mutation rate ranges from 8.9 × 10 to 7.5 × 10 per locus per generation. Microsatellite mutation rates vary with base position relative to
4558-704: The "strong correlation between linguistic and genetic diversity" and signs of relatedness between the Beja and the peoples of the Horn of Africa such as the Amhara and Oromo. On the other hand, the Masalit and Fur live in Darfur and speak a Nilo-Saharan language. The authors observed in their study that "the Masalit possesses by far the highest frequency of the E-M78 and of the E-V32 haplogroup", which they believe suggests "either
4664-442: The "strong correlation between linguistic and genetic diversity" and signs of relatedness between the Beja and the peoples of the Horn of Africa such as the Amhara and Oromo. On the other hand, the Masalit and Fur live in Darfur and speak a Nilo-Saharan language. The authors observed in their study that "the Masalit possesses by far the highest frequency of the E-M78 and of the E-V32 haplogroup", which they believe suggests "either
4770-885: The Arabian Peninsula E-V32 Found in Somalia and the Arabian Peninsula E-CTS10132 Found primarily in Gambia E-CTS4004 Large clade, found all over Europe and West Asia. E-V13* (E1b1b1a1b1a*) The majority of E-V13, and more generally of E-M78 in Europe. () () (E1b1b1a1b1a1) (E1b1b1a1b1a2a) (E1b1b1a1a1b1a3) In this small branch, the M35 mutation has been reversed and lost. () (E1b1b1a1b1a4) (E1b1b1a1b1a5a1) E-V22* (E1b1b1a1b2*) Found in Egypt, Arabia,
4876-478: The Arabian Peninsula E-V32 Found in Somalia and the Arabian Peninsula E-CTS10132 Found primarily in Gambia E-CTS4004 Large clade, found all over Europe and West Asia. E-V13* (E1b1b1a1b1a*) The majority of E-V13, and more generally of E-M78 in Europe. () () (E1b1b1a1b1a1) (E1b1b1a1b1a2a) (E1b1b1a1a1b1a3) In this small branch, the M35 mutation has been reversed and lost. () (E1b1b1a1b1a4) (E1b1b1a1b1a5a1) E-V22* (E1b1b1a1b2*) Found in Egypt, Arabia,
4982-509: The E-V13 subclade which appears to have entered Europe at some time undetermined from the Near East , where it apparently originated, via the Balkans . Coming to similar conclusions as the Cruciani and Trombetta team, Battaglia et al. (2008) , writing prior to the discovery of E-V68, describe Egypt as "a hub for the distribution of the various geographically localized M78-related sub-clades" and, based on archaeological data, they propose that
5088-453: The E-V13 subclade which appears to have entered Europe at some time undetermined from the Near East , where it apparently originated, via the Balkans . Coming to similar conclusions as the Cruciani and Trombetta team, Battaglia et al. (2008) , writing prior to the discovery of E-V68, describe Egypt as "a hub for the distribution of the various geographically localized M78-related sub-clades" and, based on archaeological data, they propose that
5194-694: The FLO1 gene control the level of adhesion to substrates. Short sequence repeats also provide rapid evolutionary change to surface proteins in pathenogenic bacteria; this may allow them to keep up with immunological changes in their hosts. Length changes in short sequence repeats in a fungus ( Neurospora crassa ) control the duration of its circadian clock cycles. Length changes of microsatellites within promoters and other cis-regulatory regions can change gene expression quickly, between generations. The human genome contains many (>16,000) short sequence repeats in regulatory regions, which provide 'tuning knobs' on
5300-529: The Horn of Africa were dominated by relatively recent branches (see E-V32 below). They concluded that the region of Egypt was the likely place of origin of E-M78 based on "the peripheral geographic distribution of the most derived subhaplogroups with respect to northeastern Africa, as well as the results of quantitative analysis of UEP and microsatellite diversity". Cruciani et al. (2007) also note this as evidence for "a corridor for bidirectional migrations" between Northeast Africa (Egypt and Libya in their data) on
5406-529: The Horn of Africa were dominated by relatively recent branches (see E-V32 below). They concluded that the region of Egypt was the likely place of origin of E-M78 based on "the peripheral geographic distribution of the most derived subhaplogroups with respect to northeastern Africa, as well as the results of quantitative analysis of UEP and microsatellite diversity". Cruciani et al. (2007) also note this as evidence for "a corridor for bidirectional migrations" between Northeast Africa (Egypt and Libya in their data) on
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#17327811942675512-533: The Horn of Africa), E-V68 is also observed in other parts of the continent at lower frequencies due to more recent dispersals. It is thus found today in pockets of the African Great Lakes and Southern Africa owing to early Afro-Asiatic-speaking settlers from the Horn region, and as far west as Guinea-Bissau , where its presence has been tentatively attributed to trans-Saharan movements of people from North Africa. The distribution of E-V68 in Europe
5618-461: The Horn of Africa), E-V68 is also observed in other parts of the continent at lower frequencies due to more recent dispersals. It is thus found today in pockets of the African Great Lakes and Southern Africa owing to early Afro-Asiatic-speaking settlers from the Horn region, and as far west as Guinea-Bissau , where its presence has been tentatively attributed to trans-Saharan movements of people from North Africa. The distribution of E-V68 in Europe
5724-573: The Horn of Africa, and Semitic speakers in the Near-East. He noted that variants are also found in the Aegean and Balkans, but the origin of the M35 subclade was in East Africa , and its clades were dominant in a core portion of Afro-Asiatic speaking populations which included Cushitic , Egyptian and Berber groups, in contrast Semitic speakers showed a decline in frequency going west to east in
5830-442: The Horn. These lineages are present in Egyptians, Berbers, Cushitic speakers from the Horn of Africa, and Semitic speakers in the Near-East. He noted that variants are also found in the Aegean and Balkans, but the origin of the M35 subclade was in East Africa , and its clades were dominant in a core portion of Afro-Asiatic speaking populations which included Cushitic , Egyptian and Berber groups, in contrast Semitic speakers showed
5936-1051: The Levant, and in Iraq in smaller frequencies. (E1b1b1a1b2a1) () (E1b1b1a1a2) Associated with the Maghreb, but also found in Italy and Spain. (E1b1b1a1c) Found in two individuals in Greece by Battaglia et al. 2008 So far, three individuals who are in E-V68 but not E-M78 have been reported in Sardinia, by Trombetta et al. (2011) , when announcing the discovery of V68. E-M78 is widely distributed in North Africa , Horn of Africa , West Asia (stretching as far as Southern Asia ), and Europe . The most basal and rare E-M78* paragroup has been found at its highest frequencies in Egyptians from
6042-621: The Levant, and in Iraq in smaller frequencies. (E1b1b1a1b2a1) () (E1b1b1a1a2) Associated with the Maghreb, but also found in Italy and Spain. (E1b1b1a1c) Found in two individuals in Greece by Battaglia et al. 2008 So far, three individuals who are in E-V68 but not E-M78 have been reported in Sardinia, by Trombetta et al. (2011) , when announcing the discovery of V68. E-M78 is widely distributed in North Africa , Horn of Africa , West Asia (stretching as far as Southern Asia ), and Europe . The most basal and rare E-M78* paragroup has been found at its highest frequencies in Egyptians from
6148-478: The Levantine-Syria region. Keita identified high frequencies of M35 (>50%) among Omotic populations, but stated that this derived from a small, published sample of 12. Keita also wrote that the PN2 mutation was shared by M35 and M2 lineages and this defined clade originated from East Africa. He concluded that "the genetic data give population profiles that clearly indicate males of African origin, as opposed to being of Asian or European descent" but acknowledged that
6254-546: The M78 mutation) only in Sardinia , and not in the Middle Eastern samples. Concerning E-M78, like other forms of E-V68 there is evidence of multiple routes of expansion out of an African homeland. On the other hand, while there were apparently direct migrations from North Africa to Iberia and Southern Italy (of people carrying E-V68*, E-V12, E-V22, and E-V65), the majority of E-M78 lineages found in Europe belong to
6360-427: The M78 mutation) only in Sardinia , and not in the Middle Eastern samples. Concerning E-M78, like other forms of E-V68 there is evidence of multiple routes of expansion out of an African homeland. On the other hand, while there were apparently direct migrations from North Africa to Iberia and Southern Italy (of people carrying E-V68*, E-V12, E-V22, and E-V65), the majority of E-M78 lineages found in Europe belong to
6466-427: The analysis or raw nextgen DNA sequencing reads to determine the genotype and variants at repetitive loci. Microsatellites can be analysed and verified by established PCR amplification and amplicon size determination, sometimes followed by Sanger DNA sequencing . In forensics, the analysis is performed by extracting nuclear DNA from the cells of a sample of interest, then amplifying specific polymorphic regions of
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#17327811942676572-492: The biodiversity does not indicate any specific set of skin colors or facial features as populations were subject to microevolutionary pressures. Loosdrecht et al. (2018) analysed genome-wide data from seven ancient Iberomaurusian individuals from the Grotte des Pigeons near Taforalt in eastern Morocco . The fossils were directly dated to between 15,100 and 13,900 calibrated years before present. The scientists found that all
6678-438: The biodiversity does not indicate any specific set of skin colors or facial features as populations were subject to microevolutionary pressures. Loosdrecht et al. (2018) analysed genome-wide data from seven ancient Iberomaurusian individuals from the Grotte des Pigeons near Taforalt in eastern Morocco . The fossils were directly dated to between 15,100 and 13,900 calibrated years before present. The scientists found that all
6784-604: The discovery of the defining SNP, Cruciani et al. (2007) reported that V12* was found in its highest concentrations in Egypt, especially Southern Egypt. Hassan et al. (2008) report a significant presence of E-V12* in neighboring Sudan, including 5/33 Copts and 5/39 Nubians . E-V12* made up approximately 20% of the Sudanese E-M78. They propose that the E-V12 and E-V22 sub-clades of E-M78 might have been brought to Sudan from their place of origin in North Africa after
6890-479: The discovery of the defining SNP, Cruciani et al. (2007) reported that V12* was found in its highest concentrations in Egypt, especially Southern Egypt. Hassan et al. (2008) report a significant presence of E-V12* in neighboring Sudan, including 5/33 Copts and 5/39 Nubians . E-V12* made up approximately 20% of the Sudanese E-M78. They propose that the E-V12 and E-V22 sub-clades of E-M78 might have been brought to Sudan from their place of origin in North Africa after
6996-417: The early observation that centrifugation of genomic DNA in a test tube separates a prominent layer of bulk DNA from accompanying "satellite" layers of repetitive DNA. They are widely used for DNA profiling in cancer diagnosis , in kinship analysis (especially paternity testing ) and in forensic identification. They are also used in genetic linkage analysis to locate a gene or a mutation responsible for
7102-433: The early observation that centrifugation of genomic DNA in a test tube separates a prominent layer of bulk DNA from accompanying "satellite" layers of repetitive DNA. The increasing availability of DNA amplification by PCR at the beginning of the 1990s triggered a large number of studies using the amplification of microsatellites as genetic markers for forensic medicine, for paternity testing, and for positional cloning to find
7208-438: The enzyme responsible for reading DNA during replication, can slip while moving along the template strand and continue at the wrong nucleotide. DNA polymerase slippage is more likely to occur when a repetitive sequence (such as CGCGCG) is replicated. Because microsatellites consist of such repetitive sequences, DNA polymerase may make errors at a higher rate in these sequence regions. Several studies have found evidence that slippage
7314-602: The expression of many genes. Length changes in bacterial SSRs can affect fimbriae formation in Haemophilus influenzae , by altering promoter spacing. Dinucleotide microsatellites are linked to abundant variation in cis-regulatory control regions in the human genome. Microsatellites in control regions of the Vasopressin 1a receptor gene in voles influence their social behavior, and level of monogamy. In Ewing sarcoma (a type of painful bone cancer in young humans),
7420-873: The extracted DNA by means of the polymerase chain reaction . Once these sequences have been amplified, they are resolved either through gel electrophoresis or capillary electrophoresis , which will allow the analyst to determine how many repeats of the microsatellites sequence in question there are. If the DNA was resolved by gel electrophoresis, the DNA can be visualized either by silver staining (low sensitivity, safe, inexpensive), or an intercalating dye such as ethidium bromide (fairly sensitive, moderate health risks, inexpensive), or as most modern forensics labs use, fluorescent dyes (highly sensitive, safe, expensive). Instruments built to resolve microsatellite fragments by capillary electrophoresis also use fluorescent dyes. Forensic profiles are stored in major databanks. The British data base for microsatellite loci identification
7526-774: The formation of tetrapods and to represent an artifact of an RNA world . Almost 50% of the human genome is contained in various types of transposable elements (also called transposons, or 'jumping genes'), and many of them contain repetitive DNA. It is probable that short sequence repeats in those locations are also involved in the regulation of gene expression. Microsatellites are used for assessing chromosomal DNA deletions in cancer diagnosis. Microsatellites are widely used for DNA profiling , also known as "genetic fingerprinting", of crime stains (in forensics) and of tissues (in transplant patients). They are also widely used in kinship analysis (most commonly in paternity testing). Also, microsatellites are used for mapping locations within
7632-598: The gene underlying a trait or disease. Prominent early applications include the identifications by microsatellite genotyping of the eight-year-old skeletal remains of a British murder victim ( Hagelberg et al. 1991), and of the Auschwitz concentration camp doctor Josef Mengele who escaped to South America following World War II ( Jeffreys et al. 1992). A microsatellite is a tract of tandemly repeated (i.e. adjacent) DNA motifs that range in length from one to six or up to ten nucleotides (the exact definition and delineation to
7738-479: The generations and gives rise to variability that can be used for DNA fingerprinting and identification purposes. Other microsatellites are located in regulatory flanking or intronic regions of genes, or directly in codons of genes – microsatellite mutations in such cases can lead to phenotypic changes and diseases, notably in triplet expansion diseases such as fragile X syndrome and Huntington's disease . Telomeres are linear sequences of DNA that sit at
7844-401: The genome and can be isolated from semi-degraded DNA of older specimens, as all that is needed is a suitable substrate for amplification through PCR. More recent techniques involve using oligonucleotide sequences consisting of repeats complementary to repeats in the microsatellite to "enrich" the DNA extracted ( microsatellite enrichment ). The oligonucleotide probe hybridizes with the repeat in
7950-620: The genome, specifically in genetic linkage analysis to locate a gene or a mutation responsible for a given trait or disease. As a special case of mapping, they can be used for studies of gene duplication or deletion . Researchers use microsatellites in population genetics and in species conservation projects. Plant geneticists have proposed the use of microsatellites for marker assisted selection of desirable traits in plant breeding. In tumour cells, whose controls on replication are damaged, microsatellites may be gained or lost at an especially high frequency during each round of mitosis . Hence
8056-447: The longer minisatellites varies from author to author), and are typically repeated 5–50 times. For example, the sequence TATATATATA is a dinucleotide microsatellite, and GTCGTCGTCGTCGTC is a trinucleotide microsatellite (with A being Adenine , G Guanine , C Cytosine , and T Thymine ). Repeat units of four and five nucleotides are referred to as tetra- and pentanucleotide motifs, respectively. Most eukaryotes have microsatellites, with
8162-426: The main subclades of M78 as of June 2015. Within the E-M78 subclade, Trombetta et al. 2015 allocated most of the former E-M78* chromosomes to three new distinct branches: E-V1083*, E-V1477 and E-V259. The first is a paragroup sister to clades E-V22 and E-V13. The mutation V1477 defines a new basal branch observed only in one northern African sample. Finally, a sister clade of E-V12, defined by V264, includes E-V65 and
8268-426: The main subclades of M78 as of June 2015. Within the E-M78 subclade, Trombetta et al. 2015 allocated most of the former E-M78* chromosomes to three new distinct branches: E-V1083*, E-V1477 and E-V259. The first is a paragroup sister to clades E-V22 and E-V13. The mutation V1477 defines a new basal branch observed only in one northern African sample. Finally, a sister clade of E-V12, defined by V264, includes E-V65 and
8374-676: The male specimens with sufficient nuclear DNA preservation belonged to the E1b1b1a1 (M78) subclade, with one skeleton bearing the E1b1b1a1b1 parent lineage to E-V13. Martiniano et al. (2022) later reassigned all the Taforalt samples to haplogroup E-M78 and none to E-L618, the predecessor to EV13. Battaglia et al. (2008) estimated that E-M78 (called E1b1b1a1 in that paper) has been in Europe longer than 10,000 years. And more recently, Lacan et al. (2011) found that human remains excavated in
8480-503: The male specimens with sufficient nuclear DNA preservation belonged to the E1b1b1a1 (M78) subclade, with one skeleton bearing the E1b1b1a1b1 parent lineage to E-V13. Martiniano et al. (2022) later reassigned all the Taforalt samples to haplogroup E-M78 and none to E-L618, the predecessor to EV13. Battaglia et al. (2008) estimated that E-M78 (called E1b1b1a1 in that paper) has been in Europe longer than 10,000 years. And more recently, Lacan et al. (2011) found that human remains excavated in
8586-401: The microsatellite, and the probe/microsatellite complex is then pulled out of solution. The enriched DNA is then cloned as normal, but the proportion of successes will now be much higher, drastically reducing the time required to develop the regions for use. However, which probes to use can be a trial and error process in itself. ISSR (for inter-simple sequence repeat ) is a general term for
8692-924: The microsatellite, repeat type, and base identity. Mutation rate rises specifically with repeat number, peaking around six to eight repeats and then decreasing again. Increased heterozygosity in a population will also increase microsatellite mutation rates, especially when there is a large length difference between alleles. This is likely due to homologous chromosomes with arms of unequal lengths causing instability during meiosis. Many microsatellites are located in non-coding DNA and are biologically silent. Others are located in regulatory or even coding DNA – microsatellite mutations in such cases can lead to phenotypic changes and diseases. A genome-wide study estimates that microsatellite variation contributes 10–15% of heritable gene expression variation in humans. In mammals, 20–40% of proteins contain repeating sequences of amino acids encoded by short sequence repeats. Most of
8798-607: The notable exception of some yeast species. Microsatellites are distributed throughout the genome. The human genome for example contains 50,000–100,000 dinucleotide microsatellites, and lesser numbers of tri-, tetra- and pentanucleotide microsatellites. Many are located in non-coding parts of the human genome and therefore do not produce proteins, but they can also be located in regulatory regions and coding regions . Microsatellites in non-coding regions may not have any specific function, and therefore might not be selected against; this allows them to accumulate mutations unhindered over
8904-541: The one hand and East Africa on the other. Because Cruciani et al. (2007) also proposed that E-M35, the parent clade of E-M78, originated in East Africa during the Palaeolithic and subsequently spread to the region of Egypt. E-M78 in East Africa, is therefore the result of a back migration. The authors believe there were "at least 2 episodes between 23.9–17.3 ky and 18.0–5.9 ky ago". Another probable migration to
9010-420: The one hand and East Africa on the other. Because Cruciani et al. (2007) also proposed that E-M35, the parent clade of E-M78, originated in East Africa during the Palaeolithic and subsequently spread to the region of Egypt. E-M78 in East Africa, is therefore the result of a back migration. The authors believe there were "at least 2 episodes between 23.9–17.3 ky and 18.0–5.9 ky ago". Another probable migration to
9116-530: The physical and chemical properties of proteins, with the potential for producing gradual and predictable changes in protein action. For example, length changes in tandemly repeating regions in the Runx2 gene lead to differences in facial length in domesticated dogs ( Canis familiaris ), with an association between longer sequence lengths and longer faces. This association also applies to a wider range of Carnivora species. Length changes in polyalanine tracts within
9222-717: The point of origin of E-M78 (as opposed to later dispersals from Egypt) may have been in a refugium which "existed on the border of present-day Sudan and Egypt, near Lake Nubia , until the onset of a humid phase around 8500 BC. The northward-moving rainfall belts during this period could have also spurred a rapid migration of Mesolithic foragers northwards in Africa, the Levant and ultimately onwards to Asia Minor and Europe, where they each eventually differentiated into their regionally distinctive branches". The division of E-V68 into sub-clades such as E-V12, E-V13, etc. has largely been
9328-612: The point of origin of E-M78 (as opposed to later dispersals from Egypt) may have been in a refugium which "existed on the border of present-day Sudan and Egypt, near Lake Nubia , until the onset of a humid phase around 8500 BC. The northward-moving rainfall belts during this period could have also spurred a rapid migration of Mesolithic foragers northwards in Africa, the Levant and ultimately onwards to Asia Minor and Europe, where they each eventually differentiated into their regionally distinctive branches". The division of E-V68 into sub-clades such as E-V12, E-V13, etc. has largely been
9434-570: The potentially useful microsatellites are determined, the flanking sequences can be used to design oligonucleotide primers which will amplify the specific microsatellite repeat in a PCR reaction. Random microsatellite primers can be developed by cloning random segments of DNA from the focal species. These random segments are inserted into a plasmid or bacteriophage vector , which is in turn implanted into Escherichia coli bacteria. Colonies are then developed, and screened with fluorescently–labelled oligonucleotide sequences that will hybridize to
9540-1007: The progressive desertification of the Sahara around 6,000–8,000 years ago. Sudden climate change might have forced several Neolithic cultures/people to migrate northward to the Mediterranean and southward to the Sahel and the Nile Valley. The E-V12* paragroup is also observed in Europe (e.g. amongst French Basques ) and Eastern Anatolia (e.g. Erzurum Turks ). The non-basal subhaplogroup E1b1b-V12/E3b1a1 has been found at highest frequencies among various Afroasiatic-speaking populations in eastern Africa, including Garreh (74.1%), Gabra (58.6%), Wata (55.6%), Borana (50.0%), Sanye (41.7%), Beja (33.3%) and Rendille (29.0%). E-M224 has been found in Israel among Yemeni population (5%) and appears to be
9646-723: The progressive desertification of the Sahara around 6,000–8,000 years ago. Sudden climate change might have forced several Neolithic cultures/people to migrate northward to the Mediterranean and southward to the Sahel and the Nile Valley. The E-V12* paragroup is also observed in Europe (e.g. amongst French Basques ) and Eastern Anatolia (e.g. Erzurum Turks ). The non-basal subhaplogroup E1b1b-V12/E3b1a1 has been found at highest frequencies among various Afroasiatic-speaking populations in eastern Africa, including Garreh (74.1%), Gabra (58.6%), Wata (55.6%), Borana (50.0%), Sanye (41.7%), Beja (33.3%) and Rendille (29.0%). E-M224 has been found in Israel among Yemeni population (5%) and appears to be
9752-423: The purity of the canonical repeated sequence. A variety of mechanisms for mutation of microsatellite loci have been reviewed, and their resulting polymorphic nature has been quantified. The actual cause of mutations in microsatellites is debated. One proposed cause of such length changes is replication slippage, caused by mismatches between DNA strands while being replicated during meiosis . DNA polymerase ,
9858-532: The replicated segment. With the abundance of PCR technology, primers that flank microsatellite loci are simple and quick to use, but the development of correctly functioning primers is often a tedious and costly process. If searching for microsatellite markers in specific regions of a genome, for example within a particular intron , primers can be designed manually. This involves searching the genomic DNA sequence for microsatellite repeats, which can be done by eye or by using automated tools such as repeat masker . Once
9964-445: The short sequence repeats within protein-coding portions of the genome have a repeating unit of three nucleotides, since that length will not cause frame-shifts when mutating. Each trinucleotide repeating sequence is transcribed into a repeating series of the same amino acid. In yeasts, the most common repeated amino acids are glutamine, glutamic acid, asparagine, aspartic acid and serine. Mutations in these repeating segments can affect
10070-599: The south from Egypt was noted by Hassan et al. (2008) based upon their survey of Sudan. Specifically E-V12 and E-V22, "might have been brought to Sudan from North Africa after the progressive desertification of the Sahara around 6,000-8,000 years ago". Northwards from Egypt and Libya, E-M78 migrated into the Middle East, but additionally Trombetta et al. (2011) proposed that the earlier E-V68 carrying population may have migrated by sea directly from Africa to southwestern Europe, because they observed cases of E-V68* (without
10176-539: The south from Egypt was noted by Hassan et al. (2008) based upon their survey of Sudan. Specifically E-V12 and E-V22, "might have been brought to Sudan from North Africa after the progressive desertification of the Sahara around 6,000-8,000 years ago". Northwards from Egypt and Libya, E-M78 migrated into the Middle East, but additionally Trombetta et al. (2011) proposed that the earlier E-V68 carrying population may have migrated by sea directly from Africa to southwestern Europe, because they observed cases of E-V68* (without
10282-404: The study refers specifically to the region of Egypt and Libya . Prior to Cruciani et al. (2007) , Semino et al. (2004) had proposed a place of origin for E-M78 further south in East Africa . This was because of the high frequency and diversity of E-M78 lineages in the region of Ethiopia. However, Cruciani et al. (2007) were able to study more data, and concluded that the E-M78 lineages in
10388-403: The study refers specifically to the region of Egypt and Libya . Prior to Cruciani et al. (2007) , Semino et al. (2004) had proposed a place of origin for E-M78 further south in East Africa . This was because of the high frequency and diversity of E-M78 lineages in the region of Ethiopia. However, Cruciani et al. (2007) were able to study more data, and concluded that the E-M78 lineages in
10494-461: The updated phylogenies found in Karafet et al. (2008) , and ISOGG , which is in turn the basis of the phylogeny given below. Keita (2008) examined a published Y-chromosome dataset on Afro-Asiatic populations and found that a key lineage E-M35 / E-M78 , sub-clade mutation of haplogroup E, was shared between the populations in the locale of original Egyptian speakers and modern Cushitic speakers from
10600-651: The very ends of chromosomes and protect the integrity of genomic material (not unlike an aglet on the end of a shoelace) during successive rounds of cell division due to the "end replication problem". In white blood cells, the gradual shortening of telomeric DNA has been shown to inversely correlate with ageing in several sample types. Telomeres consist of repetitive DNA, with the hexanucleotide repeat motif TTAGGG in vertebrates. They are thus classified as minisatellites . Similarly, insects have shorter repeat motifs in their telomeres that could arguably be considered microsatellites. Unlike point mutations , which affect only
10706-400: The work of an Italian team including Fulvio Cruciani, Beniamino Trombetta, Rosario Scozzari and others. They started on the basis of STR studies in 2004, and then in 2006 they announced the discoveries of single nucleotide polymorphism (SNP) mutations which could define most of the main branches with better clarity, which was then discussed further in 2007. These articles were the basis of
10812-474: The work of an Italian team including Fulvio Cruciani, Beniamino Trombetta, Rosario Scozzari and others. They started on the basis of STR studies in 2004, and then in 2006 they announced the discoveries of single nucleotide polymorphism (SNP) mutations which could define most of the main branches with better clarity, which was then discussed further in 2007. These articles were the basis of the updated phylogenies found in Karafet et al. (2008) , and ISOGG , which
10918-641: The workhorse genetic markers for genome-wide scans to locate any gene responsible for a given phenotype or disease, using segregation observations across generations of a sampled pedigree. Although the rise of higher throughput and cost-effective single-nucleotide polymorphism (SNP) platforms led to the era of the SNP for genome scans, microsatellites remain highly informative measures of genomic variation for linkage and association studies. Their continued advantage lies in their greater allelic diversity than biallelic SNPs, thus microsatellites can differentiate alleles within
11024-794: Was found only in two subjects from Egypt (3.6%) and in one Arab from Morocco". Sanchez et al. (2005) found it extremely prominent in Somali men and stated that "the male Somali population is a branch of the Horn African population – closely related to the Oromos in Ethiopia and North Kenya (Boranas)" and that their gamma cluster lineages "probably were introduced into the Somali population 4000–5000 years ago". More recently, Tillmar et al. (2009) typed 147 males from Somalia for 12 Y-STR loci, and observed that 77% (113/147) had typical E-V32 haplotypes. This
11130-571: Was found only in two subjects from Egypt (3.6%) and in one Arab from Morocco". Sanchez et al. (2005) found it extremely prominent in Somali men and stated that "the male Somali population is a branch of the Horn African population – closely related to the Oromos in Ethiopia and North Kenya (Boranas)" and that their gamma cluster lineages "probably were introduced into the Somali population 4000–5000 years ago". More recently, Tillmar et al. (2009) typed 147 males from Somalia for 12 Y-STR loci, and observed that 77% (113/147) had typical E-V32 haplotypes. This
11236-532: Was originally based on the British SGM+ system using 10 loci and a sex marker . The Americans increased this number to 13 loci. The Australian database is called the NCIDD, and since 2013 it has been using 18 core markers for DNA profiling. Microsatellites can be amplified for identification by the polymerase chain reaction (PCR) process, using the unique sequences of flanking regions as primers . DNA
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