The Genetic Legacy of the Expansion of Turkic-Speaking Nomads Across Eurasia

Bayazit Yunusbayev, Mait Metspalu, Ene Metspalu, Albert Valeev, Sergei Litvinov, Ruslan Valiev, Vita Akhmetova, Elena Balanovska, Oleg Balanovsky, Shahlo Turdikulova, Dilbar Dalimova, Pagbajabyn Nymadawa, Ardeshir Bahmanimehr, Hovhannes Sahakyan, Kristiina Tambets, Sardana Fedorova, Nikolay Barashkov, Irina Khidiatova, Evelin Mihailov, Rita Khusainova, Larisa Damba, Miroslava Derenko, Boris Malyarchuk, Ludmila Osipova, Mikhail Voevoda, Levon Yepiskoposyan, Toomas Kivisild, Elza Khusnutdinova, Richard Villems
doi: http://dx.doi.org/10.1101/005850

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghanistan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language?s expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. Most of the Turkic peoples studied, except those in Central Asia, genetically resembled their geographic neighbors, in agreement with the elite dominance model of language expansion. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area where historians center a series of early Turkic and non-Turkic steppe polities. The observed excess of long chromosomal tracts IBD (> 1cM) between populations from SSM and Turkic peoples across West Eurasia was statistically significant. Finally, we used the ALDER method and inferred admixture dates (~9th?17th centuries) that overlap with the Turkic migrations of the 5th?16th centuries. Thus, our results indicate historical admixture among Turkic peoples, and the recent shared ancestry with modern populations in SSM supports one of the hypothesized homelands for their nomadic Turkic and related Mongolic ancestors.

MIPSTR: a method for multiplex genotyping of germ-line and somatic STR variation across many individuals
Keisha Dawn Carlson, Peter H Sudmant, Maximilian Oliver Press, Evan E Eichler, Jay Shendure, Christine Queitsch

Abstract Short tandem repeats (STRs) are highly mutable genetic elements that often reside in functional genomic regions. The cumulative evidence of genetic studies on individual STRs suggests that STR variation profoundly affects phenotype and contributes to trait heritability. Despite recent advances in sequencing technology, STR variation has remained largely inaccessible across many individuals compared to single nucleotide variation or copy number variation. STR genotyping with short-read sequence data is confounded by (1) the difficulty of uniquely mapping short, low-complexity reads and (2) the high rate of STR amplification stutter. Here, we present MIPSTR, a robust, scalable, and affordable method that addresses these challenges. MIPSTR uses targeted capture of STR loci by single-molecule Molecular Inversion Probes (smMIPs) and a unique mapping strategy. Targeted capture and mapping strategy resolve the first challenge; the use of single molecule information resolves the second challenge. Unlike previous methods, MIPSTR is capable of distinguishing technical error due to amplification stutter from somatic STR mutations. In proof-of-principle experiments, we use MIPSTR to determine germ-line STR genotypes for 102 STR loci with high accuracy across diverse populations of the plant A. thaliana. We show that putatively functional STRs may be identified by deviation from predicted STR variation and by association with quantitative phenotypes. Employing DNA mixing experiments and a mutant deficient in DNA repair, we demonstrate that MIPSTR can detect low-frequency somatic STR variants. MIPSTR is applicable to any organism with a high-quality reference genome and is scalable to genotyping many thousands of STR loci in thousands of individuals.

An estimate of the average number of recessive lethal mutations carried by humans
Ziyue Gao, Darrel Waggoner, Matthew Stephens, Carole Ober, Molly Przeworski
(Submitted on 28 Jul 2014)

The effects of inbreeding on human health depend critically on the number and severity of recessive, deleterious mutations carried by individuals. In humans, existing estimates of these quantities are based on comparisons between consanguineous and non-consanguineous couples, an approach that confounds socioeconomic and genetic effects of inbreeding. To circumvent this limitation, we focused on a founder population with almost complete Mendelian disease ascertainment and a known pedigree. By considering all recessive lethal diseases reported in the pedigree and simulating allele transmissions, we estimated that each haploid set of human autosomes carries on average 0.29 (95% credible interval [0.10, 0.83]) autosomal, recessive alleles that lead to complete sterility or severe disorders at birth or before reproductive age when homozygous. Comparison to existing estimates of the deleterious effects of all recessive alleles suggests that a substantial fraction of the burden of autosomal, recessive variants is due to single mutations that lead to death between birth and reproductive age. In turn, the comparison to estimates from other eukaryotes points to a surprising constancy of the average number of recessive lethal mutations across organisms with markedly different genome sizes.