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. 2023 Sep;142(9):1327-1343.
doi: 10.1007/s00439-023-02579-5. Epub 2023 Jun 14.

Population history modulates the fitness effects of Copy Number Variation in the Roma

Marco Antinucci  1 , David Comas  1 , Francesc Calafell  2
Affiliations

Population history modulates the fitness effects of Copy Number Variation in the Roma

Marco Antinucci et al. Hum Genet. 2023 Sep.

Abstract

We provide the first whole genome Copy Number Variant (CNV) study addressing Roma, along with reference populations from South Asia, the Middle East and Europe. Using CNV calling software for short-read sequence data, we identified 3171 deletions and 489 duplications. Taking into account the known population history of the Roma, as inferred from whole genome nucleotide variation, we could discern how this history has shaped CNV variation. As expected, patterns of deletion variation, but not duplication, in the Roma followed those obtained from single nucleotide polymorphisms (SNPs). Reduced effective population size resulting in slightly relaxed natural selection may explain our observation of an increase in intronic (but not exonic) deletions within Loss of Function (LoF)-intolerant genes. Over-representation analysis for LoF-intolerant gene sets hosting intronic deletions highlights a substantial accumulation of shared biological processes in Roma, intriguingly related to signaling, nervous system and development features, which may be related to the known profile of private disease in the population. Finally, we show the link between deletions and known trait-related SNPs reported in the genome-wide association study (GWAS) catalog, which exhibited even frequency distributions among the studied populations. This suggests that, in general human populations, the strong association between deletions and SNPs associated to biomedical conditions and traits could be widespread across continental populations, reflecting a common background of potentially disease/trait-related CNVs.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
UMAP plots for deletions copy numbers. UMAP plots representing samples dataset labeled with regional assignation (A) and dataset of origin (B)
Fig. 2
Fig. 2
FST values for pairs of populations. For each pair of population, genome-wide Fst values are shown for deletions (A), duplications (B), and SNPs (C). Top quintile VST values distribution for deletions and duplications, by pairs of populations and genomic location (D)
Fig. 3
Fig. 3
Abundance distribution and statistical tests results for deletions among populations. Statistical test and multiple comparisons results for intergenic (A) and intronic (B) deletions and their relative number distribution among populations
Fig. 4
Fig. 4
Number of categorized GO terms among populations
See this image and copyright information in PMC

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