A genome-wide characterization of copy number variations in native populations of Peninsular Malaysia

Fu, Ruiqing; Mokhtar, Siti Shuhada; Phipps, Maude E.; Hoh, Boon Peng; Xu, Shuhua

doi:10.1038/s41431-018-0120-8

Cited by 13 publications

(11 citation statements)

References 43 publications

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“…In order to understand the extent to which CNVs influence phenotypes, deep analyses in both patient and healthy individuals are required. Different approaches, including quantification of hybridization to specific oligonucleotides 13 , clone arrays 14 , direct genome sequencing 15,16 , and single-nucleotide polymorphism (SNP) array [17][18][19] , allowed to explore CNVs, thus providing their global estimates of frequencies, distribution, and functional features in large population cohorts and HapMap samples 1,2,4,16,[19][20][21][22][23][24][25][26][27][28][29] . Although medical and clinical genetic studies have been widely performed in the Arab World known to display high rates of consanguinity and endogamy, little attention has been paid to potential variations linked to health in the region 30,31 .…”

Section: Introductionmentioning

confidence: 99%

A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

et al. 2021

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Copy number variation (CNV) is considered as the most frequent type of structural variation in the human genome. Some CNVs can act on human phenotype diversity, encompassing rare Mendelian diseases and genomic disorders. The North African populations remain underrepresented in public genetic databases in terms of single-nucleotide variants as well as for larger genomic mutations. In this study, we present the first CNV map for a North African population using the Affymetrix Genome-Wide SNP (single-nucleotide polymorphism) array 6.0 array genotyping intensity data to call CNVs in 102 Tunisian healthy individuals. Two softwares, PennCNV and Birdsuite, were used to call CNVs in order to provide reliable data. Subsequent bioinformatic analyses were performed to explore their features and patterns. The CNV map of the Tunisian population includes 1083 CNVs spanning 61.443 Mb of the genome. The CNV length ranged from 1.017 kb to 2.074 Mb with an average of 56.734 kb. Deletions represent 57.43% of the identified CNVs, while duplications and the mixed loci are less represented. One hundred and three genes disrupted by CNVs are reported to cause 155 Mendelian diseases/phenotypes. Drug response genes were also reported to be affected by CNVs. Data on genes overlapped by deletions and duplications segments and the sequence properties in and around them also provided insights into the functional and health impacts of CNVs. These findings represent valuable clues to genetic diversity and personalized medicine in the Tunisian population as well as in the ethnically similar populations from North Africa.

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Section: Introductionmentioning

confidence: 99%

A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

et al. 2021

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“…To better catalog the full extent of genetic variation across human populations, targeted analyses of genetic variation in under-represented populations are needed. Several recent studies have undertaken such analyses, including of single-nucleotide variations (SNVs), small insertion-deletions (indels), and copy number variations (CNVs) in under-represented populations including people of African, Asian, Latinx and Native American ancestry [29,[51][52][53][54][55][56][57][58][59]. Here, we present a catalog of genome-wide copy number variations in a large cohort of healthy individuals of African ancestry.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide copy number variations in a large cohort of bantu African children

et al. 2021

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Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. Methods We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. Results We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. Conclusions These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

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“…However, these native populations are largely underrepresented in the whole-genome sequencing projects. The genomic architecture of these populations were characterized by a handful of SNP-array-based genome-wide studies [17–22]. Recently, using the whole genome sequencing data of 12 unrelated individuals, we have also revealed the population structure and divergence between native populations from Peninsular Malaysia and North Borneo [23].…”

Section: Introductionmentioning

confidence: 99%

Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations

et al. 2019

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BackgroundRecent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated.ResultsWe analyzed the whole-genome deep sequencing data (~ 30×) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81 × 10− 8 – 1.33 × 10− 8, 1.0 × 10− 9 – 2.9 × 10− 9, and ~ 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples.ConclusionOur study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia.

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A genome-wide characterization of copy number variations in native populations of Peninsular Malaysia

Cited by 13 publications

References 43 publications

A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa

Genome-wide copy number variations in a large cohort of bantu African children

Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations

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