Human Parental Relatedness through Time - Detecting Runs of Homozygosity in Ancient DNA

Abstract

We present a novel method to detect runs of homozygosity (ROH) from low-coverage genotype data typical for ancient human DNA. ROH are the genetic signature of matings between related parents, and as such, the frequency and length distribution of these blocks can give insight into recent population history and mating patterns. Existing methods identify ROH by scanning for regions that lack heterozygote genotypes, but this strategy frequently fails for ancient individuals: The vast majority of ancient DNA data has low read depth (ă3ˆ), which makes reliable diploid genotype calling infeasible. To overcome this limitation, we make use of linkage disequilibrium information from a panel of modern reference haplotypes using a Hidden Markov Model. Our method scans for long stretches where the read data are consistent with only a single haplotype. When tested on simulated and down-sampled pseudo-haploid data from a targeted set of 1.24 million single nucleotide polymorphisms ("1240k SNPs") widely used in ancient DNA, our implementation robustly works for coverage down to 0.5ˆand can tolerate error rates up to 3%, with high power and low false positive rate for blocks longer than 4 centiMorgans. Therefore, the method can screen a substantial fraction of human genome-wide ancient DNA data for parental relatedness, which will yield new evidence for questions regarding past demography and social organization.

Ancient genomes reveal structural shifts after the arrival of Steppe-related ancestry in the Italian Peninsula

“…To further explore these scenarios, we analyzed ROHs (STAR Methods) in the ancient and selected modern populations (TSI; Figures 4A-4C; Data S5C) with hap-ROH, which is a method to detect ROH segments in lowcoverage genomes using a haplotype reference panel (STAR Methods). 61 We checked that differences in coverage did not systematically bias estimates (Figure 4D) and checked against imputation and sequencing errors (STAR Methods; Figure S7; Data S5B). We calculated segment number and length in four length categories: <1.6 centimorgan (cM); >1.6 cM; >4 cM; and >8 cM (Data S5C) and focus on the greater than 1.6 cM length category (which includes 4 and 8 cM segments), which is informative regarding recent consanguinity and is the most reliably inferred (STAR Methods; Figure S5; Data S5).…”

ContamLD: estimation of ancient nuclear DNA contamination using breakdown of linkage disequilibrium

“…In principle, this inbreeding effect could be corrected explicitly by estimating the total amount of ROH in each individual and applying this as a correction, although we do not provide such functionality as part of our software. A reliable methodology for quantifying the proportion of the genome that is affected by inbreeding in ancient individuals has now become available (hapRHO), [18] and ContamLD could be further improved by using an estimate of ROH from software like this as an input parameter.…”

Long runs of homozygosity are correlated with marriage preferences across global population samples

“…Based on the analytical result derived in [18], we expect, on average, ≈ 6 ROH longer than 10cM in a population where all unions were between cousins; ≈ 9 if all of them are first cousins. Our simulations confirm that both the average total length and the number of ROH (of all lengths) increase as a function of increasing degree of consanguinity as well as the number of generations for which the practice continues.…”

“…We also calculated the expected number and total length of long runs of homozygosity analytically using the model described in [18]. Briefly, there are m = 2n + 4 meioses separating the two chromosomes of an offspring of n th cousins.…”

“…Briefly, there are m = 2n + 4 meioses separating the two chromosomes of an offspring of n th cousins. For such an offspring, the number of segments of length x in the i th chromosome of length l i (in Morgans) has the following density (Equation S8 of [18]):…”