Family-Based Whole Genome Sequencing Identified Novel Variants in ABCA5 Gene in a Patient with Idiopathic Ventricular Tachycardia

AbstractIn studies of families with rare disease, it is common to screen for de novo mutations, as well as recessive or dominant variants that explain the phenotype. However, the filtering strategies and software used to prioritize high-confidence variants vary from study to study. In an effort to establish recommendations for rare disease research, we explore effective guidelines for variant (SNP and INDEL) filtering and report the expected number of candidates for de novo dominant, recessive, and autosomal dominant modes of inheritance. We derived these guidelines using two large family-based cohorts that underwent whole-genome sequencing, as well as two family cohorts with whole-exome sequencing. The filters are applied to common attributes, including genotype-quality, sequencing depth, allele balance, and population allele frequency. The resulting guidelines yield ~10 candidate SNP and INDEL variants per exome, and 18 per genome for recessive and de novo dominant modes of inheritance, with substantially more candidates for autosomal dominant inheritance. For family-based, whole-genome sequencing studies, this number includes an average of three de novo, ten compound heterozygous, one autosomal recessive, four X-linked variants, and roughly 100 candidate variants following autosomal dominant inheritance. The slivar software we developed to establish and rapidly apply these filters to VCF files is available at https://github.com/brentp/slivar under an MIT license, and includes documentation and recommendations for best practices for rare disease analysis.

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A comparison of whole genome sequencing with exome sequencing for family-based association studies

BMC Proceedings ◽

10.1186/1753-6561-8-s1-s38 ◽

2014 ◽

Vol 8 (S1) ◽

Cited By ~ 10

Author(s):

Sean Lacey ◽

Jae Yoon Chung ◽

Honghuang Lin

Keyword(s):

Whole Genome Sequencing ◽

Exome Sequencing ◽

Genome Sequencing ◽

Association Studies ◽

Whole Genome ◽

Family Based

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NyuWa Genome Resource: Deep Whole Genome Sequencing Based Chinese Population Variation Profile and Reference Panel

10.1101/2020.11.10.376574 ◽

2020 ◽

Author(s):

Peng Zhang ◽

Huaxia Luo ◽

Yanyan Li ◽

You Wang ◽

Jiajia Wang ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Chinese Population ◽

Population Variation ◽

Reference Panel ◽

Specific Reference ◽

Whole Genome ◽

Loss Of Function ◽

Southern Chinese ◽

Novel Variants

AbstractThe lack of Chinese population specific haplotype reference panel and whole genome sequencing resources has greatly hindered the genetics studies in the world’s largest population. Here we presented the NyuWa genome resource of 71.1M SNPs and 8.2M indels based on deep (26.2X) sequencing of 2,999 Chinese individuals, and constructed NyuWa reference panel of 5,804 haplotypes and 19.3M variants, which is the first publicly available Chinese population specific reference panel with thousands of samples. There were 25.0M novel variants in NyuWa genome resource, and 3.2M specific variants in NyuWa reference panel. Compared with other panels, NyuWa reference panel reduces the Han Chinese imputation error rate by the range of 30% to 51%. Population structure and imputation simulation tests supported the applicability of one integrated reference panel for both northern and southern Chinese. In addition, a total of 22,504 loss-of-function variants in coding and noncoding genes were identified, including 11,493 novel variants. These results highlight the value of NyuWa genome resource to facilitate genetics research in Chinese and Asian populations.

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Whole genome sequencing data of multiple individuals of Pakistani descent

Scientific Data ◽

10.1038/s41597-020-00664-2 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Shahid Y. Khan ◽

Muhammad Ali ◽

Mei-Chong W. Lee ◽

Zhiwei Ma ◽

Pooja Biswas ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Sequence Data ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Asian Populations ◽

Ethnic Populations ◽

Novel Variants ◽

Intergenic Regions

Abstract Here we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.

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