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BackgroundThe Parsis, one of the smallest religious community in the world, reside in South Asia. Previous genetic studies on them, although based on low resolution markers, reported both Iranian and Indian ancestries. To understand the population structure and demographic history of this group in more detail, we analyzed Indian and Pakistani Parsi populations using high-resolution autosomal and uniparental (Y-chromosomal and mitochondrial DNA) markers. Additionally, we also assayed 108 mitochondrial DNA markers among 21 ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India.ResultsOur extensive analyses indicated that among present-day populations, the Parsis are genetically closest to Middle Eastern (Iranian and the Caucasus) populations rather than their South Asian neighbors. They also share the highest number of haplotypes with present-day Iranians and we estimate that the admixture of the Parsis with Indian populations occurred ∼1,200 years ago. Enriched homozygosity in the Parsi reflects their recent isolation and inbreeding. We also observed 48% South-Asian-specific mitochondrial lineages among the ancient samples, which might have resulted from the assimilation of local females during the initial settlement.ConclusionsWe show that the Parsis are genetically closest to the Neolithic Iranians, followed by present-day Middle Eastern populations rather than those in South Asia and provide evidence of sex-specific admixture from South Asians to the Parsis. Our results are consistent with the historically-recorded migration of the Parsi populations to South Asia in the 7thcentury and in agreement with their assimilation into the Indian sub-continent’s population and cultural milieu “like sugar in milk”. Moreover, in a wider context our results suggest a major demographic transition in West Asia due to Islamic-conquest.

Multiple questions relating to contributions of cultural and demographical factors in the process of human geographical dispersal remain largely unanswered. India, a land of early human settlement and the resulting diversity is a good place to look for some of the answers. In this study, we explored the genetic structure of India using a diverse panel of 78 males genotyped using the GenoChip. Their genome-wide single-nucleotide polymorphism (SNP) diversity was examined in the context of various covariates that influence Indian gene pool. Admixture analysis of genome-wide SNP data showed high proportion of the Southwest Asian component in all of the Indian samples. Hierarchical clustering based on admixture proportions revealed seven distinct clusters correlating to geographical and linguistic affiliations. Convex hull overlay of Y-chromosomal haplogroups on the genome-wide SNP principal component analysis brought out distinct non-overlapping polygons of F*-M89, H*-M69, L1-M27, O2a-M95 and O3a3c1-M117, suggesting a male-mediated migration and expansion of the Indian gene pool. Lack of similar correlation with mitochondrial DNA clades indicated a shared genetic ancestry of females. We suggest that ancient male-mediated migratory events and settlement in various regional niches led to the present day scenario and peopling of India.

We have assessed copy number variation (CNV) in the male-specific part of the human Y chromosome discovered by array comparative genomic hybridization (array-CGH) in 411 apparently healthy UK males, and validated the findings using SNP genotype intensity data available for 149 of them. After manual curation taking account of the complex duplicated structure of Y-chromosomal sequences, we discovered 22 curated CNV events considered validated or likely, mean 0.93 (range 0–4) per individual. 16 of these were novel. Curated CNV events ranged in size from 3 Mb, and in frequency from 1/411 to 107/411. Of the 24 protein-coding genes or gene families tested, nine showed CNV. These included a large duplication encompassing the AMELY and TBL1Y genes that probably has no phenotypic effect, partial deletions of the TSPY cluster and AZFc region that may influence spermatogenesis, and other variants with unknown functional implications, including abundant variation in the number of RBMY genes and/or pseudogenes, and a novel complex duplication of two segments overlapping the AZFa region and including the 3′ end of the UTY gene. Erratum (https://dx.doi.org/10.1007%2Fs00439-015-1565-2): The second author’s initial was missing, and the fifth to eighth authors’ initials were incorrect. The correct names are Tomas W. Fitzgerald, Blair H. Smith, Anna F. Dominiczak, Andrew D. Morris, and David J. Porteous. The complete author list is given below: Wei Wei, Tomas W. Fitzgerald, Qasim Ayub, Andrea Massaia, Blair H. Smith, Anna F. Dominiczak, Andrew D. Morris, David J. Porteous, Matthew E. Hurles, Chris Tyler-Smith, Yali Xue

We present a new method, Fine-Mapping of Adaptive Variation (FineMAV), which combines population differentiation, derived allele frequency, and molecular functionality to prioritize positively selected candidate variants for functional follow-up. We calibrate and test FineMAV using eight experimentally validated “gold standard” positively selected variants and simulations. FineMAV has good sensitivity and a low false discovery rate. Applying FineMAV to the 1000 Genomes Project Phase 3 SNP dataset, we report many novel selected variants, including ones in TGM3 and PRSS53 associated with hair phenotypes that we validate using available independent data. FineMAV is widely applicable to sequence data from both human and other species. Electronic supplementary material The online version of this article (10.1186/s13059-017-1380-2) contains supplementary material, which is available to authorized users.

Nature Communications 5: Article number: 3513 (2014); Published: 29 April 2016; Updated: 31 October 2016 This article was published without any competing financial interests statement. A revised declaration that lists potentially competing financial interests is provided below: A.D.M., M.M. and M.A.are affiliated with Bcs Biotech S.

Islam is the second most practiced religion in India, next to Hinduism. It is still unclear whether the spread of Islam in India has been only a cultural transformation or is associated with detectable levels of gene flow. To estimate the contribution of West Asian and Arabian admixture to Indian Muslims, we assessed genetic variation in mtDNA, Y-chromosomal and LCT/MCM6 markers in 472, 431 and 476 samples, respectively, representing six Muslim communities from different geographical regions of India. We found that most of the Indian Muslim populations received their major genetic input from geographically close non-Muslim populations. However, low levels of likely sub-Saharan African, Arabian and West Asian admixture were also observed among Indian Muslims in the form of L0a2a2 mtDNA and E1b1b1a and J(*)(xJ2) Y-chromosomal lineages. The distinction between Iranian and Arabian sources was difficult to make with mtDNA and the Y chromosome, as the estimates were highly correlated because of similar gene pool compositions in the sources. In contrast, the LCT/MCM6 locus, which shows a clear distinction between the two sources, enabled us to rule out significant gene flow from Arabia. Overall, our results support a model according to which the spread of Islam in India was predominantly cultural conversion associated with minor but still detectable levels of gene flow from outside, primarily from Iran and Central Asia, rather than directly from the Arabian Peninsula.

The Y-STR DYS19 is firmly established in the repertoire of Y-chromosomal markers used in forensic analysis yet is poorly understood at the molecular level, lying in a complex genomic environment and exhibiting null alleles, as well as duplications and occasional triplications in population samples. Here, we analyse three null alleles and 51 duplications and show that DYS19 can also be involved in inversion events, so that even its location within the short arm of the Y chromosome is uncertain. Deletion mapping in the three chromosomes carrying null alleles shows that their deletions are less than approximately 300 kb in size. Haplotypic analysis with binary markers shows that they belong to three different haplogroups and so represent independent events. In contrast, a collection of 51 DYS19 duplication chromosomes belong to only four haplogroups: two are singletons and may represent somatic mutation in lymphoblastoid cell lines, but two, in haplogroups G and C3c, represent founder lineages that have spread widely in Central Europe/West Asia and East Asia, respectively. Consideration of candidate mechanisms underlying both deletions and duplications provides no evidence for the involvement of non-allelic homologous recombination, and they are likely to represent sporadic events with low mutation rates. Understanding the basis and population distribution of these DYS19 alleles will aid in the utilisation and interpretation of profiles that contain them.

The presence of Africans in Britain has been recorded since Roman times, but has left no apparent genetic trace among modern inhabitants. Y chromosomes belonging to the deepest-rooting clade of the Y phylogeny, haplogroup (hg) A, are regarded as African-specific, and no examples have been reported from Britain or elsewhere in Western Europe. We describe the presence of an hgA1 chromosome in an indigenous British male; comparison with African examples suggests a Western African origin. Seven out of 18 men carrying the same rare east-Yorkshire surname as the original male also carry hgA1 chromosomes, and documentary research resolves them into two genealogies with most-recent-common-ancestors living in Yorkshire in the late 18th century. Analysis using 77 Y-short tandem repeats (STRs) is consistent with coalescence a few generations earlier. Our findings represent the first genetic evidence of Africans among 'indigenous' British, and emphasize the complexity of human migration history as well as the pitfalls of assigning geographical origin from Y-chromosomal haplotypes.

We have established 16 small multiplex reactions of two–four loci to amplify 52 recently described single-copy simple Y-STRs and typed these loci in a worldwide panel of 74 diverse men and two women. Two Y-STRs were found to be commonly multicopy in this sample set and were excluded from the study. Of the remaining 50, four (DYS481, DYS570, DYS576 and DYS643) showed higher diversities than the commonly used loci and can potentially provide increased haplotype discrimination in both forensic and anthropological work. Ten loci showed occasional missing alleles, duplicated peaks or intermediate-sized alleles. Electronic supplementary material Supplementary material is available for this article at http://dx.doi.org/10.1007/s00414-006-0124-8 and is accessible for authorized users.

Biallelic polymorphisms on the Y chromosome have been extensively used to study the history, evolution, and migration patterns of world populations. In this study we screened 8.5 kb of Y chromosomal DNA for single nucleotide polymorphisms (SNPs) in a panel of 95 male individuals belonging to different haplogroups. Five novel Y-SNPs (PK1-5) were identified, four in the Pakistani sample and one in an African sample. The ancestral state of each SNP was determined in two chimpanzee samples and a variety of Pakistani ethnic groups. In addition to these novel Y-SNPs 77 additional markers on the Y chromosome were analyzed to place the SNPs on the phylogenetic tree of Y chromosomal lineages and to further investigate extant human Y chromosomal variation within Pakistan. BATWING analysis gave an estimate of between 2,500 and 7,300 YBP for population expansion in Pakistan which coincides with the period of the Indus Valley civilizations.

We have analyzed 11 Y-STR loci (DYS19, the two DYS385 loci, DYS388, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DXYS156Y) in 700 males from ten ethnic groups in east Asia in order to evaluate their usefulness for forensic and population genetic studies. A total of 644 different haplotypes were identified, among which 603 (86.14%) were individual-specific. The haplotype diversity averaged over all populations was 0.9997; using only the nine Y-STRs comprising the "minimal haplotype" (excluding DYS388 and DXYS156Y) it was 0.9996, a value similar to that found in 1924 samples from other Asian populations (0.9996; Lessig et al. Legal Medicine 5(2003) 160-163), and slightly higher than in European populations (0.9976; n=11,610; Roewer et al. For Sci International (2001) 118:103-111). All of the individual east Asian populations examined here had high haplotype diversity (or =0.997), except for the Mongolians (0.992) and Manchurians (0.960). The most frequent haplotype identified by the nine markers was present at only 1% (7/700). Population comparisons based on Phi(ST) or rho genetic distance measures revealed clustering according to the traditional northeast-southeast distinction, but with exceptions. For example, the Yunnan population from southern China lay among the northern populations, possibly reflecting recent migration, while the Korean population, traditionally considered northern, lay at the boundary between northern and southern populations. An admixture estimate suggested 55(51-59)% northern, 45(41-49)% southern contribution to the Koreans, illustrating the complexity of the genetic history of this region.

Until recently, the Y chromosome seemed to fulfil the role of juvenile delinquent among human chromosomes — rich in junk, poor in useful attributes, reluctant to socialize with its neighbours and with an inescapable tendency to degenerate. The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution. Y-chromosome research is growing up.

During the past few years, the DNA Commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area - namely, Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.

We describe a novel rearranged human Y chromosome consisting of an inverted duplication of the long arm heterochromatin and a small amount of euchromatin: rea(Y)(qter-q11.2::q11.2-qter). The normal centromere has been deleted and a neocentromere containing CENP-A, -C, -E and Mad2 but not CENP-B has formed close to the breakpoint. A 2.7 Mb yeast artificial chromosome contig spanning the breakpoint was constructed and the breakpoint was localised to a region of

The sequence of a second chimpanzee Y chromosome has been determined. It confirms the degradation of four genes on the chimpanzee lineage, reveals the recent gain of one on the human lineage and emphasizes the low Y-chromosomal genetic diversity within western chimpanzees.

Correction to: Journal of Human Genetics (2016) 61, 593–603; doi:10.1038/jhg.2016.26; published online 31 March 2016 After online publication of this article, an error was identified in the list of authors. This error has been rectified and the corrected article appears in this issue. The html and online pdf versions have also been rectified.

We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other. Electronic supplementary material The online version of this article (doi:10.1007/s00439-011-1111-9) contains supplementary material, which is available to authorized users.

The online version of the original article can be found under doi:10.1007/s00439-015-1562-5.

A report on the 'Genomic Disorders 2013: from 60 years of DNA to human genomes in the clinic' meeting, held at Homerton College, Cambridge, UK, April 10-12, 2013.

Next-generation sequencing technologies have produced many 'whole' human genome sequences and the 1000 Genomes Project is poised to add two and a half thousand additional genomes. The 1000 Genomes Pilot 1 Project has sequenced Y chromosomes from 77 males (27 CEU, 10 CHB, 16 JPT, 24 YRI) albeit at low (1x-2x) sequence coverage, and identified a total of ~3000 variable sites of which 75% are novel. Although many sites are missed, preliminary validation by Sanger di-deoxy sequencing gave an initial estimate of a low (3.3%) false positive rate. In addition, we have developed a resource of Y-specific primer pairs that target single-copy regions of the human Y chromosome. These have been used to produce 5-7 kb overlapping fragments by long-PCR that are subsequently pooled and sequenced. This strategy was used to sequence, at high depth, 2-3 Mb of single-copy Y-specific DNA in a haplogroup A individual. The primer pairs have also been distributed to the wider community with the aim of re-sequencing comparable targeted regions in a diverse group of Y chromosomes. Using these primers, we have also established a tag indexing protocol that uses an 8-bp tag specific to each male, so that pooled samples from several males can be sequenced in one lane of an Illumina Genome Analyzer II, and sequence reads can be assigned back to each male sample using the tag. Using these approaches, we aim to generate individual Y-chromosomal sequences with adequate coverage that can be appropriately filtered to generate robust Y-SNP calls for refinement of the Y phylogenetic tree and further investigation of lineages of particular interest.

There is a long-standing historical controversy over the question of US President Thomas Jefferson's paternity of the children of Sally Hemings, one of his slaves1,4. To throw some scientific light on the dispute, we have compared Y-chromosomal DNA haplotypes from male-line descendants of Field Jefferson, a paternal uncle of Thomas Jefferson, with those of male-line descendants of Thomas Woodson, Sally Hemings' putative first son, and of Eston Hemings Jefferson, her last son. The molecular findings fail to support the belief that Thomas Jefferson was Thomas Woodson's father, but provide evidence that he was the biological father of Eston Hemings Jefferson.

It is true that men of Randolph Jefferson's family could have fathered Sally Hemings’ later children. Space constraints prevented us from expanding on alternative interpretations of our DNA analysis, including the interesting one proposed by Davis. The title assigned to our study was misleading in that it represented only the simplest explanation of our molecular findings: namely, that Thomas Jefferson, rather than one of the Carr brothers, was likely to have been the father of Eston Hemings Jefferson.