Aye Ko Ko Minn et al. 他は日本人
Nature>Journal of Human Genetics
03 April 2025
①日本人だけを対象にNROH（数）を分析している。他民族集団との比較がなされていない
②NROH（数）分析で、味覚、嗅覚等が検出されているものの、他民族との比較分析がないため、日本人固有かどうかは、不明である。例えば、苦味という味覚は狩猟採取民にとって人類共通で必要である。
Abstract
In the study, we searched for ROHs in two high-coverage WGS datasets from 3552 Japanese individuals and 192 three-generation families (consisting of 1120 family members) in prospective genomic cohorts.
he results showed that a considerable number of ROHs, especially short ones that may have remained undetected in conventionally used SNP-array data, can be detected in the WGS data.
Additionally, we identified gene families within ROH islands that are associated with enriched pathways related to sensory perception of taste and odors, suggesting potential signatures of selection in these key genomic regions.
Introduction
Previous studies demonstrated that modern Japanese and ancient Jomon individuals exhibit a relatively high average total length of ROH, especially in shorter categories (≤500 KB) [1,2,3].Ceballos et al. have shown that ROHs are not uniformly distributed across the human genome. Instead, ROHs tend to cluster within the specific genomic regions, forming ROH islands, the genomic locations of which can vary depending on ethnicities or genetic backgrounds [19].
19は、下記レビュー論文
Runs of homozygosity: windows into population history and trait architecture
In this study, we applied two high-coverage whole-genome sequencing datasets: 3.5KJPNv2—a dataset constructed from a haplotype frequency panel of 3552 Japanese individuals [20], and BirThree—a dataset along with pedigree information of 1120 Japanese individuals, derived from Birth and Three-generation Cohort Study [21], which can allow us to more precisely identify shorter ROH segments by taking into account the effects of sequencing errors.
To illustrate the large advantages provided by WGS datasets, we investigated the detectability of ROHs down to very low minimum length, at the kilobase level, in the Japanese population.
Results
We investigated the detectability of ROH under different analytical approaches and assessed the SNP-density and functional effects, using biobank-level scale Japanese WGS datasets [20,21,22,23] and major bioinformatic tools [7, 11].
We have compared length intervals of detected ROH, and for both BCFtools and PLINK, we observed a higher prevalence of ROHs between 100 KB and 1.5 Mb at all variant sites compared to the array-based sites (Fig. 1 and S1A–B). However, we noticed that longer ROHs (>1.5 Mb) are more abundant in array-based sites compared to all variant sites in both tools (Fig. 1).
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ROH > 1.5 Mb (3.5KJPNv2 dataset)
We set a minimal ROH length of 1.5 Mb to detect longer ROHs per-individual and investigated the NROH and SROH accordingly.
We detected a consistent pattern, as seen in analysis of total numbers of ROH segments, where ROH1500 are more prevalent in the array-specific regions than in all variant sites by using both BCFtools and PLINK (Table 1, Fig. 2A).
).
ROH > 1.5 Mb (BirThree dataset)
We next analyzed the dataset from the Tohoku Medical Megabank (TMM) Project BirThree Cohort (Table 2, Fig. 2B).
In contrast to the 3.5KJPNv2 dataset, BCFtools detected more ROH1500 segments across all variant sites (mean NROH1500 of 10.44 and SROH1500 of 27.5 Mbp) than in the array-specific regions of the BirThree dataset.
A comprehensive evaluation of ROH segments, comparing distributions of numerous ROH lengths between all variant sites and array specific sites showed smaller dissimilarities in the BirThree dataset (Fig. S4E–H).
Our analysis revealed enriched pathways related to three main gene families that are prominently involved in ROH island regions detected by BCFtools.
First, the USP17 family of genes showed significant presence in pathways related to protein deubiquitination, proteolysis, and cell apoptosis.
Second, several members of the TAS2R family (TAS2R14, TAS2R20, TAS2R30, TAS2R31, TAS2R43, TAS2R46, TAS2R50) were identified within ROH islands on chromosome 12 in the BirThree dataset and these were associated with taste receptor activity, taste transduction, and sensory perception of taste pathways (Fig. 3 and S2A, Table S2A).
Additionally, ROH islands located in regions containing genes such as HADHA, HADHB, IP6K1, and IP6K2, which are involved in enzymatic activity linked to fatty acid metabolism and inositol phosphate synthesis were also identified by PLINK (Fig. 3 and S2A–B) (Tables S2B–C and F).
Additionally, we also examined the genomic-based inbreeding coefficient (FROH) to unravel the validity of our results, using the same method as previously described [13]. By doing this, we obtained the array-based sites result (FROH > 1.5 MB = 0.010064) consistent with that of a previous Clark et al.
Discussion
ROHs are distributed over a wide range of genomic regions in many species. Modern humans have substantially lower genetic diversity, i.e., an estimated effective population size of only about 10,000, compared with other species, and are thus expected to have many ROHs.
Notwithstanding that the efficiency and effectiveness of WGS technologies are remarkable, applying the technologies in unrelated individuals may result in relatively high probability of error rates [26].
Genomic based inbreeding coefficient (FROH) was estimated by dividing the cumulative length of all ROH segments in an individual's genome by the total length of the autosomal genome [13]. We also conducted the stratification analysis, grouping ROH segments into the different bins of size (S4A–H).
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