title: Deep whole-genome sequencing of 100 southeast Asian Malays.
abstract: Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Lai-Ping
authors.initials: LP
authors.lastname: Wong
authors.forename: Rick Twee-Hee
authors.initials: RT
authors.lastname: Ong
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Poh
authors.forename: Xuanyao
authors.initials: X
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Ruoying
authors.initials: R
authors.lastname: Li
authors.forename: Kevin Koi-Yau
authors.initials: KK
authors.lastname: Lam
authors.forename: Nisha Esakimuthu
authors.initials: NE
authors.lastname: Pillai
authors.forename: Kar-Seng
authors.initials: KS
authors.lastname: Sim
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Ngak-Leng
authors.initials: NL
authors.lastname: Sim
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Teo
authors.forename: Jia-Nee
authors.initials: JN
authors.lastname: Foo
authors.forename: Linda Wei-Lin
authors.initials: LW
authors.lastname: Tan
authors.forename: Yenly
authors.initials: Y
authors.lastname: Lim
authors.forename: Seok-Hwee
authors.initials: SH
authors.lastname: Koo
authors.forename: Linda Seo-Hwee
authors.initials: LS
authors.lastname: Gan
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: Sharon
authors.initials: S
authors.lastname: Wee
authors.forename: Eric Peng-Huat
authors.initials: EP
authors.lastname: Yap
authors.forename: Pauline Crystal
authors.initials: PC
authors.lastname: Ng
authors.forename: Wei-Yen
authors.initials: WY
authors.lastname: Lim
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: Markus Rene
authors.initials: MR
authors.lastname: Wenk
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Peter
authors.initials: P
authors.lastname: Little
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
mesh_terms: D044466:Asian People / Q000235:genetics*; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008296:Malaysia; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics; D012846:Singapore