The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals

Cao, Yanan; Li, Lin; Xu, Min; Feng, Zhihui; Sun, Xiaohui; Lu, Jieli; Xu, Yu; Du, Peina; Wang, Tiange; Hu, Ruying; Ye, Zhen; Shi, Lixin; Tang, Xulei; Li, Yan; Gao, Zhengnan; Chen, Gang; Zhang, Yinfei; Chen, Lulu; Ning, Guang; Bi, Yufang; Wang, Weiqing

doi:10.1038/s41422-020-0322-9

Cited by 182 publications

(157 citation statements)

References 81 publications

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“…In an attempt to better understand the susceptibility of different populations to infection by SARS-CoV-2, we gathered data on ACE2 missense variants from different projects and databases that aggregate allele frequencies (AF). These projects and databases include Single Nucleotide Polymorphism Database (dbSNP) [ 8 ], 1000 genomes project phase 3 (1KGP3) [ 9 ], Allele Frequency Aggregator (ALFA project) a , Exome Aggregation Consortium (ExAC) [ 10 ], genome Aggregation Database (gnomAD) [ 11 ], GO exome sequencing project (ESP) b , Trans-Omics for Precision Medicine (TopMed) [ 12 ], in addition to a recent study reporting data from the China Metabolic Analytics Project (ChinaMAP) and other populations [ 13 , 14 ].…”

Section: Resultsmentioning

confidence: 99%

ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

Ali¹,

Elserafy²,

Alkordi³

et al. 2020

Biochemistry and Biophysics Reports

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The susceptibility of different populations to SARS-CoV-2 infection is not yet understood. Here, we combined ACE2 coding variants' analysis in different populations and computational chemistry calculations to probe the effects on SARS-CoV-2/ACE2 interaction. ACE2-K26R; which is most frequent in Ashkenazi Jewish population decreased the SARS-CoV-2/ACE2 electrostatic attraction. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R increased the electrostatic attraction; ordered by binding strength from weakest to strongest. The aforementioned variants are most frequent in East Asian, South Asian, African and African American, European, European and South Asian populations, respectively.

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Section: Resultsmentioning

confidence: 99%

ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

Ali¹,

Elserafy²,

Alkordi³

et al. 2020

Biochemistry and Biophysics Reports

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“…Familial segregation demonstrated a de novo mutation. This variant was not found in gnomAD, mbiobank [32], ClinVar or the Human Gene Mutation Database (HGMD) (2019.4) or included in the literature on the comprehensive pathogenic mutation spectrum [33]. According to the ACMG guidelines, the variant is classified as pathogenic considering PVS1, PM2, and PM6 [34].…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemia and Dandy-Walker variant in a Kabuki syndrome patient: a case report

Guo

Zhao

et al. 2020

BMC Med Genet

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Background Kabuki syndrome (KS) is a rare congenital condition with cardinal manifestations of typical facial features, developmental delays, skeletal anomalies, abnormal dermatoglyphic presentations, and mild to moderate intellectual disability. Pathogenic variants in two epigenetic modifier genes, KMT2D and KDM6A, are responsible for KS1 and KS2, respectively. Case presentation A Chinese girl had persistent neonatal hypoglycemia and Dandy-Walker variant. Whole-exome sequencing identified a novel single nucleotide deletion in KMT2D (NM_003482.3 c.12165del p.(Glu4056Serfs*10)) that caused frameshift and premature termination. The mutation was de novo. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is considered pathogenic. The patient was diagnosed with KS by molecular testing. Conclusion A single novel mutation in KMT2D was identified in a KS patients with hypoglycemia and Dandy-Walker variant in the neonatal stage. A molecular test was conducted to diagnose KS at an early stage.

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“…Reference control data were obtained from GnomAD (https://gnomad.broadinstitute.org/), 22 which contained exome or genome sequencing data from 141 456 unrelated individuals and mBiobank (http://www.mbiobank.com/), 23 which contained genome sequencing data of 10 588 samples from the China Metabolic Analytics Project (ChinaMAP). The low‐quality variants in the GnomAD were excluded, and we only included the East Asian populations (N = 9977) in the GnomAD considering the ethnic specificity.…”

Section: Methodsmentioning

confidence: 99%

Prevalence of comprehensive DNA damage repair gene germline mutations in Chinese prostate cancer patients

Pan

et al. 2020

Intl Journal of Cancer

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Germline DNA damage repair (DDR) deficiency has been associated with increased cancer risk, poor prognosis and therapeutic opportunity for prostate cancer (PCa) patients. However, the landscape of germline mutations in PCa covering comprehensive DDR genes has not been reported. We performed whole‐exome sequencing in 246 patients who meet the National Cancer Center Network guidelines for genetic testing and analyzed variants in 276 DDR genes, which was from the Cancer Genome Atlas. A total of 79 deleterious germline alterations in 60 DDR genes were identified in 31% (76/246) patients. Mutations were found in nine DDR pathways, including 11.8% men in homologous recombination repair (HR) pathways, 2.4% men in mismatch repair (MMR) pathway and 16.7% (41/246) patients in non‐HR/MMR pathways. In HRR and MMR pathways, mutations were mostly identified in BRCA2 (5.3%), HFM1 (0.8%), ZSWIM7 (0.8%), MSH2 (0.8%) and MSH3 (0.8%). When compared with the cancer‐free cohort, POLN and POLG conferred high risk to PCa with odds ratio 6.9 and 20.5, respectively. We provided a comprehensive view of germline DDR gene mutations in PCa patients. We also identified two potential PCa predisposition genes: POLN and POLG, which have not been reported in the Western population, confirming the necessity of customizing a multigene panel for Chinese PCa patients.

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The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals

Cited by 182 publications

References 81 publications

ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

Hypoglycemia and Dandy-Walker variant in a Kabuki syndrome patient: a case report

Prevalence of comprehensive DNA damage repair gene germline mutations in Chinese prostate cancer patients

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