Runs of Homozygosity in sub-Saharan African populations provide insights into a complex demographic and health history

Abstract

12The study of runs of homozygosity (ROH), contiguous regions in the genome where an individual is 13 homozygous across all sites, can shed light on the demographic history and cultural practices. We present 14 a fine-scale ROH analysis of 1679 individuals from 28 sub-Saharan African (SSA) populations along with 15 1384 individuals from 17 world-wide populations. Using high-density SNP coverage, we could accurately 16 obtain ROH as low as 300Kb using PLINK software. The analyses showed a heterogeneous distribution of 17 autozygosity across SSA, revealing a complex demographic history. They highlight differences between 18African groups and can differentiate between the impact of consanguineous practices (e.g. among the 19 Somali) and endogamy (e.g. among several Khoe-San groups 1 ). The genomic distribution of ROH was 20 analysed through the identification of ROH islands and regions of heterozygosity (RHZ). These 21 2 homozygosity cold and hotspots harbour multiple protein coding genes. Studying ROH therefore not only 22 sheds light on population history, but can also be used to study genetic variation related to the health of 23 extant populations. 24 disequilibrium (LD) among markers, are not always considered autozygous but nevertheless are due to 41 the mating of distantly related individuals. A different source of apparent homozygosity, hemizygous 42 deletions, can masquerade as ROH, but such copy number variation has a minor effect in ROH studies [7][8][9] . 43 3 Since their discovery in the mid-1990s 10 ROH were found to be ubiquitous. We are all inbred to some 44 degree and ROH capture this aspect of our demographic histories, with runs of homozygosity being the 45 genomic footprint of the phenomenon known as pedigree collapse 11 . ROH are present in all populations, 46 even in admixed or outbred populations and arise by two different processes: a limited effective 47 population size (Ne) and by consanguineous unions. Independently of how they were generated, ROH can 48 be used to obtain the genomic inbreeding coefficient or FROH 7; 8 . Traditionally, the inbreeding coefficient 49 (the probability that an individual receives two alleles that are identical-by-descent at a given locus which 50 is also the expected proportion of the genome being autozygous) is obtained using pedigrees and its 51 accuracy depends on the depth and reliability of the pedigree 12; 13 . FROH measures the actual proportion of 52 the autosomal genome that is autozygous over and above a specific minimum length ROH threshold. 53When this cut-off is set at 1.5Mb, FROH correlates most strongly (r=0.86) with the F obtained from an 54 accurate six-generation pedigree (FPED) 8 . Using 20-generation depth genealogies with more than 5000 55 individuals of European Royal dynasties, with many complex inbreeding loops, it has been found that 56 above the 10 th generation the change in the coefficient of inbreeding (F) is less than 1% 14 . Also, it has been 57 found that individuals with no inbreeding loops in at least 5 generations (and probab...

Runs of Homozygosity and Gene Identification in Pelibuey Sheep Using Genomic Data

“…The genetic structure of the population was calculate using the het function in PLINK v1.9 [29]. F is the ratio of the SNP within an individual, relative to the He of the alleles and randomly drawn from the population [32]. F of an individual in subpopulation was calculated as Fis = 1 − Ho/He [33]; where He and Ho are the expected and observed heterozygotes, respectively.…”