Biology subjects

Boyko, A. R.

Publications and source records attributed to Boyko, A. R..

3 recordsLinked to original sources

bioRxiv2018

Fine-scale resolution and analysis of runs of homozygosity in domestic dogs

Abstract/SummaryInbreeding and consanguinity leave distinct genomic traces, most notably long genomic tracts that are identical by descent and completely homozygous. These runs of homozygosity (ROH) can contribute to inbreeding depression if they contain deleterious variants that are fully or partially recessive. Several lines of evidence have been used to show that long (> 5 megabase (Mb)) ROH are disproportionately likely to harbor deleterious variation, but the extent to which long versus short tracts contribute to autozygosity at loci known to be deleterious and recessive has not been studied.\n\nIn domestic dogs, nearly 200 mutations are known to cause recessive diseases, most of which can be efficiently assayed using SNP arrays. By examining genome-wide data from over 200,000 markers, including 150 recessive disease variants, we built high-resolution ROH density maps for nearly 2,500 dogs, recording ROH down to 500 kilobases. We observed over 500 homozygous deleterious recessive genotypes in the panel, 90% of which overlapped with ROH inferred by GERMLINE. Although most of these genotypes were contained in ROH over 5 Mb in length, 14% were contained in short (0.5 - 2.5 Mb) tracts, a significant enrichment compared to the genetic background, suggesting that even short tracts are useful for computing inbreeding metrics like the coefficient of inbreeding estimated from ROH (FROH).\n\nIn our dataset, FROH differed significantly both within and among dog breeds. All breeds harbored some regions of reduced genetic diversity due to drift or selective sweeps, but the degree of inbreeding and the proportion of inbreeding caused by short versus long tracts differed between breeds, reflecting their different population histories. Although only available for a few species, large genome-wide datasets including recessive disease variants hold particular promise not only for disentangling the genetic architecture of inbreeding depression, but also evaluating and improving upon current approaches for detecting ROH.

genomics↗

bioRxiv2018

Direct-To-Consumer DNA testing of 6,000 dogs reveals 98.6-kb duplication causing blue eyes and heterochromia in Siberian Huskies

Consumer genomics enables genetic discovery on an unprecedented scale by linking very large databases of personal genomic data with phenotype information voluntarily submitted via web-based surveys1. These databases are having a transformative effect on human genomic research, yielding insights on increasingly complex traits, behaviors, and disease by including many thousands of individuals in genome-wide association studies (GWAS)2, 3. The promise of consumer genomic data is not limited to human research, however. Genomic tools for dogs are readily available, with hundreds of causal Mendelian variants already characterized4-6, because selection and breeding have led to dramatic phenotypic diversity underlain by a simple genetic structure7, 8. Here, we report the results of the first consumer genomics study ever conducted in a non-human model: a GWAS of blue eyes based on more than 3,000 customer dogs with a validation panel of nearly 3,000 more, the largest canine GWAS to date. We discovered a novel association with blue eyes on chromosome 18 (P = 1x10-65) and used both sequence coverage and microarray probe intensity data to identify the putative causal variant: a 98.6-kb duplication directly upstream of the hox gene ALX4, which plays an important role in mammalian eye development9, 10. This duplication was largely restricted to Siberian Huskies and is highly, but not completely, penetrant. These results underscore the power of consumer-data-driven discovery in nonhuman species, especially dogs, where there is intense owner interest in the personal genomic information of their pets, a high level of engagement with web-based surveys, and an underlying genetic architecture ideal for mapping studies.

bioinformatics↗

bioRxiv2017

Selective sweep analysis using village dogs highlights the pivotal role of the neural crest in dog domestication

BackgroundDogs (Canis lupus familiaris) were domesticated from gray wolves between 10-40 kya in Eurasia, yet details surrounding the process of domestication remain unclear. The vast array of phenotypes exhibited by dogs mirror other domesticated animal species, a phenomenon known as the Domestication Syndrome. Here, we use signatures persisting in the dog genome to identify genes and pathways altered by the intensive selective pressures of domestication.\n\nResultsWe identified 246 candidate domestication regions containing 10.8Mb of genome sequence and 178 genes through whole-genome SNP analysis of 43 globally distributed village dogs and 10 wolves. Comparisons with ancient dog genomes suggest that these regions reflect signatures of domestication rather than breed formation. The strongest hit is located in the Retinoic Acid-Induced 1 (RAI1) gene, mutations of which cause Smith-Magenis syndrome. The identified regions contain a significant enrichment of genes linked to neural crest cell migration, differentiation and development. Read depth analysis suggests that copy number variation played a minor role in dog domestication.\n\nConclusionOur results indicate that phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development, are determined by genes which act early in embryogenesis. These differences are all phenotypes of the Domestication Syndrome, which can be explained by decreases in neural crest cells at these sites. We propose that initial selection during early dog domestication was for behavior, a trait also influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs.

evolutionary biology↗