ESHG 2008 abstracts

The European Society of Human Genetics conference is coming up, and there are some very interesting abstracts.

Note: The ESHG site has updated with a notice that the abstracts are embargoed until their presentation time. Therefore, I have decided to remove the body of this post until then, although I think it is a bit weird to embargo something that one places on the public web. In any case, you can find the abstracts easily by going to the site above. (June 1): post restored.

The peopling of North Asia: Y and X perspectives

V. A. Stepanov, V. Kharkov, I. Khitrinskaya, O. Medvedeva, M. Spiridonova, A. Marusin, V. Puzyrev; Institute for Medical Genetics, Tomsk, Russian Federation.

Presentation Number: P07.056

To reconstruct the origin and evolution of human populations in North Asia we investigated the genetic diversity in 50 population samples (about 2000 individuals totally) using Y and X chromosome lineages. Y-chromosomal haplotypes were constructed with unique event polymorphisms (UEP) and STR markers according to Y Chromosome consortium (YCC) classification. SNP markers in a single 60 kb linkage disequilibrium region of ZFX gene was used to trace the X chromosomal population history. The genetic diversity of Y haplogroups was quite high (0.70 - 0.95) in most populations except few very isolated groups. The proportion of inter-population differences in the total genetic variability measured by Fst statistics is 17% for binary haplogroups and 19% for YSTR. Multidimensional scaling and principal component analysis revealed four major components in North Asian Y gene pool, reflecting the presence of Paleoasiatic (Q), Proto-Uralic (N3, N2), Eastern Asian (O, C), and Western Eurasian (R1, I, J) lineages. X-chromosomal haplotypes in North Asia are less divers (gene diversity within populations 0.65 - 0.80) and less differentiated (Fst = 4%) compared to Y lineages. The population clustering by X and Y gives, to a first approximation, a similar picture, and matrixes of genetic distances between populations for X and Y haplotypes significantly correlates. The age of genetic diversity generation and time of population differentiation demonstrates the Upper Paleolithic origin of major Y and X lineages and post-glacial population expansions. This work is supported by RFBR grants ##06-04-48274 and 07-04-01629.

The following seems to be a very important study; in particular the notion that particular Y chromosome/mtDNA haplogroups may be associated with higher or lower fertility may have implications about their distribution.

UPDATE (May 21): I did a quick and dirty analysis of the Y-haplogroup and mtDNA-haplogroup data from Bosch et al. (2006) (Ann Hum Genet. 2006 Jul;70(Pt 4):459-87.), and there is a -0.43 correlation between Y-haplogroup I and mtDNA-haplogroup H and a +0.46 correlation between Y-haplogroup R1 and mtDNA-haplogroup H. While not significant (with only 10 populations), this is definitely in the right direction for a selection effect for/against specific Y-DNA/mtDNA combinations.

... on the other hand, another quick and dirty analysis of 23 populations from Rootsi's survey on Y-haplogroup I and mtDNA frequencies from AJHG Volume 80, Issue 4, April 2007, Pages 759-768 didn't turn up any correlation. Perhaps, someone can look at possible correlations between Y-chromosome and mtDNA haplogroups in Europe to see if anything interesting turns up.

Male infertility induced by mtDNA/Y unfavorable combination? An association study on human mitochondrial DNA

S. C. Gomes1, S. Fernandes2, R. Gonçalves1, A. T. Fernandes1, A. Barros3, H. Geada4, A. Brehm1; 1Human Genetics Laboratory, University of Madeira, Funchal, Portugal, 2Genetics Department, Faculty of Medicine, University of Porto, Porto, Portugal, 3Centre of Reproductive Genetics A Barros, Porto, Portugal, 4Faculty of Medicine, University of Lisbon, Lisboa, Portugal.

Presentation Number: P07.084

There is growing evidence that certain mtDNA haplogroups determine a genetic susceptibility to various disorders bringing out the interest in the possible role of mtDNA background on the phenotype expression of mitochondrial genetic disorders. An association between haplogroup T and asthenospermia has been reported and several sublineages of haplogroup U were associated with differences in sperm motility and vitality. The deletion of some DAZ copies gene in 10-15% of azoospermic and oligospermic patients has been reported but also present in fertile men belonging to certain Y-haplogroups. The findings of one study have rarely been replicated by studies in other populations and conflicting associations have been reported. Our focus in this case-control study is to investigate the existence of other influences, besides a weak mtDNA background, promoting male infertility. The occurrence of a specific mtDNA variant associated to a certain Y-chromosome haplogroup could represent a vital link that will compromise the sperm function and be responsible for male infertility. A group of 99 infertile men and other one composed by 90 subjects with proven fertility were selected and analysed. The frequency of the combination mtDNA-haplogroup H (especially with the CRS sequence) and Y-haplogroup R was higher in fertile than in infertile men seemingly to be favorable to fertility. On the other hand, a considerable number of infertile men belonging to mtDNA-haplogroup H (CRS) and to Y-haplogroup I, associated to a specific DAZ gene deletion pattern- 2+4d, suggests a non favorable combination to male fertility.

The Bayash Roma: phylogenetic dissection of Eurasian paternal genetic elements

I. Martinovic Klaric, M. Pericic Salihovic, L. Barac Lauc, B. Janicijevic; Institute for Anthropological Research, Zagreb, Croatia.

Presentation Number: P07.110

The Bayash consist of numerous and small Romani groups speaking different dialects of the Romanian language and living dispersedly in Croatia, Hungary, Bosnia and Herzegovina, Serbia, Romania, Bulgaria, and to the lesser extent in Macedonia, Greece, Ukraine, Slovakia and Slovenia. Larger Bayash groups migrated to Croatia most likely during the 19th century, after abolition of slavery in Romania. Molecular architecture and the origin of the Croatian Bayash paternal gene pool was addressed by analysing 151 Bayash Y chromosomes from two Croatian regions, 332 Y chromosomes from Romani populations across Europe, 814 Y-chromosomes from non-Romani host populations living in Southeastern, Southern and Eastern Europe as well as with 1680 Y-chromosomes from South Asian populations. The Bayash in Croatia represent one population of largely shared paternal genetic history characterized by substantial percentage (44%) of common H1-M82 and E3b1-M78 lineages. Relatively ancient expansion signals and limited diversity of Indian specific H1-M82 lineages imply descent from closely related paternal ancestors who could have been settled in the Indian subcontinent between 7th and 9th centuries AD. Minimal time divergence of the Bayash subpopulations is consistent with their putative migratory split within Romania towards Wallachia and Transilvania. Substantial percentage of E3b1 lineages and high associated microsatellite variance in the Bayash men is a reflection of significant admixture with majority populations from the Vardar-Morava-Danube catchment basin - possibly a common paternal signature of Romani populations in Southeastern Europe. Additional traces of admixture are evident in the modest presence of typical European haplogroups.

Are the Moravian Valachs of Czech Republic the Aromuns of Central Europe? Model population for isolation and admixture

E. Ehler1,2, V. Vančata2; 1Department of Anthropology and Human Genetics, Charles University in Prague, Faculty of Science, Prague, Czech Republic, 2Department of Biology and Ecological Education, Charles University in Prague, Faculty of Education, Prague, Czech Republic.

Presentation Number: P07.129

Moravian Valachs of Czech Republic are one of the most distinct ethnic groups from Central Europe. Related to similar populations in Poland and Slovakia, they emerge at the end of 15th century, as the north-westernmost prominence of migration that started 250 years earlier in northern Romania. Being predominately highland sheep herders and of putative Romanian origin, they represent a Central European analogue of Balkan Aromanian populations. We have gathered Y-chromosomal, linguistic, ethnographic and historical data for this population and compared them with surrounding as well as with east European populations. Linguistic data show specific parts of shared vocabulary of Romanian origin between several pastoral groups in Central and Eastern Europe. Comparing genetic and linguistic pairwise distance matrices (Mantel test) in these populations did not revealed any significant correlation. Thus we confirmed that plain geographical distance still plays the major role in genetic distances between populations in Europe. From our further analysis it is clear, that the Moravian Valachs, after at least five centuries of admixture, are not overly genetically different from surrounding populations. On the other hand, from the point of view of intra-population diversity, they are much more similar to isolated Balkan populations (e.g. Aromuns) than to Central European populations.

Phylogeography of the human Y chromosome haplogroup E3a

F. Cruciani1, B. Trombetta1, D. Sellitto2, C. Nodale1, R. Scozzari1; 1Sapienza Università di Roma, Rome, Italy, 2Consiglio Nazionale delle Ricerche, Rome, Italy.

Presentation Number: P07.134

The Y chromosome specific biallelic marker DYS271 defines the most common haplogroup (E3a) currently found in sub-Saharan Africa. A sister clade, E3b (E-M215), is rare in sub-Saharan Africa, but very common in northern and eastern Africa. On the whole, these two clades represent more than 70% of the Y chromosomes of the African continent. A third clade belonging to E3 (E3c or E-M329) has been recently reported to be present only in eastern Africa, at low frequencies. In this study we analyzed more than 1,600 Y chromosomes from 55 African populations, using both new and previously described biallelic markers, in order to refine the phylogeny and the geographic distribution of the E3a haplogroup. The most common E-DYS271 sub-clades (E-DYS271*, E-M191, E-U209) showed a non uniform distribution across sub-Saharan Africa. Most of the E-DYS271 chromosomes found in northern and western Africa belong to the paragroup E-DYS271*, which is rare in central and southern Africa. In these latter regions, haplogroups E-M191 and E-U209 show similar frequency distributions and coalescence ages (13 and 11 kyr, respectively), suggesting their involvement in the same migratory event/s. By the use of two new phylogenetically equivalent markers (V38 and V89), the earlier tripartite structure of E3 haplogroup was resolved in favor of a common ancestor for haplogroups E-DYS271 (formerly E3a) and E-M329 (formerly E3c). The new topology of the E3 haplogroup is suggestive of a relatively recent eastern African origin for the majority of the chromosomes presently found in sub-Saharan Africa.

Y-chromosome lineages in Xhosa and Zulu Bantu speaking populations

R. P. A. Gonçalves, H. Spínola, A. Brehm; Human Genetics Laboratory, Funchal, Portugal.

Presentation Number: P07.137

Y-chromosome Single Nucleotide Polymorphisms have been analysed in Zulu and Xhosa, two southern Africa Bantu speaking populations. These two ethnic groups have their origin on the farmer’s Bantu expansion from Niger-Congo border towards sub-Sahel regions on the southern tip of the continent, during the past 3000 years. Seven different Y-chromosome haplogroups were found in Zulu contrasting with only two in Xhosa. E3a, a common haplogroup among West sub-Saharans associated to Bantu migration was the most prevalent in both populations (56.9% in Zulu and 90% in Xhosa). The second most common haplogroup was E2 (29.3% in Zulu and 10% in Xhosa), present both in West and East African populations. The present-day Zulu and Xhosa paternal legacy is essentially of West sub-Saharan origin. Zulu population shows a most diverse genetic influence comparing to Xhosa, revealing some pre-Bantu expansion markers and East African influences. Zulu presents 8.6% Y-chromosome haplogroups (A, B, J1) of non-Bantu influence that could indicate gene flow from other populations, particularly Khoisan.

Human genetic population structure: Patterns and underlying processes

Presentation Time: Tuesday, 9:15 a.m. - 9:45 a.m.

G. Barbujani; University of Ferrara, Department of Biology and Evolution, Ferrara, Italy.

Presentation Number: S15.2

Classical studies of genetic diversity in humans consistently showed that the largest proportion of human diversity occurs among members of the same population. On average, differences among different populations in the same continent represent 5% of the global human variance, and differences among continents another 10%. Genetic variation is largely discordant across the genome, meaning that different loci show different spatial patterns, and implying that a good description of population structure can only be based on the analysis of multiple loci. Studies of single loci are also unlikely to reasonably identify an individual’s place of origin. A general decline of genetic of genetic diversity with distance from Africa, and a parallel increase in linkage disequilibrium, can be accounted for by the effects of a series of founder effects accompanying the spread of anatomically-modern humans from Africa. Recent DNA analyses at the global level show that most allelic variants are cosmopolitan and only a small percentage are continent-specific, whereas a clearer continental structure emerges when considering composite haplotypes. This suggests that, at the global level, gene flow has had a strong impact on genetic diversity, through both directional dispersal and successive short-range migratory exchanges. At the local level, several factors have contributed to genetic differentiation, and, in particular, language barriers have been shown to be associated with small but non-negligible increases of the genetic differences between neighboring populations.

Hierarchical analysis of 28 Y-chromosome SNP’s in the population of the Republic of Macedonia

P. Noveski, S. Trivodalieva, G. D. Efremov, D. Plaseska-Karanfilska;
Macedonian Academy of Sciences and Arts, Research Centre for Genetic Engineering and Biotechnology, Skopje, Macedonia, The Former Yugoslav Republic of.

Presentation Number: P05.211

Analysis of Y-chromosome haplogroups, defined by single nucleotide polymorphisms (SNP’s), has become a standard approach for studying the origin of human populations and measuring the variability among them. Furthermore, Y-SNP’s represent a new forensic tool, because their population specificity may allow to determine the origin of any male sample of interest for forensic purposes. The aim of this study was to develop a strategy for rapid, simple and inexpensive Y-chromosome SNP’s typing in the population of R. Macedonia. We have studied a total of 343 DNA male samples; 211 Macedonians, 111 Albanians and 21 of other ethnic origin (Roma, Serbs and Turks). Methodology included multiplex PCR and single nucleotide extension reaction by SNaPshot multiplex kit. The set of 28 markers has been grouped in 5 multiplexes in order to determine the most frequent haplogroups using only 1 or 2 multiplexes. Twenty different Y haplogroups were determined among 343 male DNA samples. The finding that five haplogroups (E3b1, I1b1, J2b1a, R1a and R1b) comprise more than 70% of the Y chromosomes is consistent with the typical European Y chromosome gene pool. The distribution of the Y-haplogroups differs between Macedonians and Albanians. The most common Y haplogroup among Macedonians is I1b1 (27.5%), followed by three haplogroups present with similar frequencies E3b1 (15.6%), R1a (14.2%) and R1b (11.4%). Among Albanians the most frequent Y haplogroup is E3b1 (28.8%), followed by R1b (18.0%), J2b1a (13.5%) and R1a (12.6%).

The following paper (probably) refers to a recent study, according to which:

One of the most elevated values of 35delG prevalence corresponds to Greece (1/28); the pattern of various 35delG prevalences is interpretated in the present meta-analysis as the result of Ancient Greek colonizations of the "Magna Grecia" in historical times.

Strong linkage disequilibrium for the frequent GJB2 35delG mutation in the Greek population
H. Kokotas¹, L. Van Laer², M. Grigoriadou¹, V. Iliadou³, J. Economides⁴, S. Pomoni¹, A. Pampanos¹, N. Eleftheriades⁵, E. Ferekidou⁶, S. Korres⁶, A. Giannoulia-Karantana⁷, G. Van Camp², M. B. Petersen¹;
¹Institute of Child Health, Athens, Greece, ²University of Antwerp, Antwerp, Belgium, ³AHEPA Hospital, Thessaloniki, Greece, ⁴‘Aghia Sophia’ Children’s Hospital, Athens, Greece, ⁵St. Loukas Hospital, Thessaloniki, Greece, ⁶Athens University, Athens, Greece, ⁷Athens University Medical School, Athens, Greece.

Presentation Number: P06.080

Approximately one in 1,000 children is affected by severe or profound hearing loss at birth or during early childhood (prelingual deafness). Up to forty percent of autosomal recessive, congenital, severe to profound hearing impairment cases result from mutations in a single gene, GJB2. The 35delG mutation accounts for the majority of GJB2 mutations detected in Caucasian populations and represents one of the most frequent disease mutations identified so far. Some previous studies have assumed that the high frequency of the 35delG mutation reflects the presence of a mutational hot spot, whilst other studies support the theory of a common founder. Greece is amongst the countries presenting high frequency of the 35delG mutation (3.5%), and a recent study raised the hypothesis of the origin of this mutation in ancient Greece. We genotyped 60 Greek deafness patients homozygous for the 35delG mutation for six single nucleotide polymorphisms (SNPs) and two microsatellite markers, mapping within or flanking the GJB2 gene, as compared to 60 Greek hearing controls. A strong linkage disequilibrium was found between the 35delG mutation and markers inside or flanking the GJB2 gene, at distances of 34 kb on the centromeric and 90 kb on the telomeric side of the gene, respectively. Our study supports the hypothesis of a founder effect and we further propose that ethnic groups of Greek ancestry could have propagated the 35delG mutation, as evidenced by historical data beginning from the 15^th century BC.