Differential analysis of mutations in the Jewish population and their implications for diseases

YARON EINHORN, DAPHNA WEISSGLAS-VOLKOV, SHAI CARMI, Harry Ostrer, EITAN FRIEDMAN, NOAM SHOMRON

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Sequencing large cohorts of ethnically homogeneous individuals yields genetic insights with implications for the entire population rather than a single individual. In order to evaluate the genetic basis of certain diseases encountered at high frequency in the Ashkenazi Jewish population (AJP), as well as to improve variant annotation among the AJP, we examined the entire exome, focusing on specific genes with known clinical implications in 128 Ashkenazi Jews and compared these data to other non-Jewish populations (European, African, South Asian and East Asian). We targeted American College of Medical Genetics incidental finding recommended genes and the Catalogue of Somatic Mutations in Cancer (COSMIC) germline cancer-related genes. We identified previously known disease-causing variants and discovered potentially deleterious variants in known disease-causing genes that are population specific or substantially more prevalent in the AJP, such as in the ATP and HGFAC genes associated with colorectal cancer and pancreatic cancer, respectively. Additionally, we tested the advantage of utilizing the database of the AJP when assigning pathogenicity to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew early-onset breast cancer (BC) patients. Importantly, population-based filtering using our AJP database enabled a reduction in the number of potential causal variants in the BC cohort by 36%. Taken together, population-specific sequencing of the AJP offers valuable, clinically applicable information and improves AJP filter annotation.

Original languageEnglish (US)
JournalGenetics Research
DOIs
StateAccepted/In press - May 15 2017

Fingerprint

Mutation
Population
Exome
Jews
Genes
Databases
Breast Neoplasms
Incidental Findings
Neoplasm Genes
Pancreatic Neoplasms
Virulence
Colorectal Neoplasms
Adenosine Triphosphate
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

EINHORN, YARON., WEISSGLAS-VOLKOV, DAPHNA., CARMI, SHAI., Ostrer, H., FRIEDMAN, EITAN., & SHOMRON, NOAM. (Accepted/In press). Differential analysis of mutations in the Jewish population and their implications for diseases. Genetics Research. https://doi.org/10.1017/S0016672317000015

Differential analysis of mutations in the Jewish population and their implications for diseases. / EINHORN, YARON; WEISSGLAS-VOLKOV, DAPHNA; CARMI, SHAI; Ostrer, Harry; FRIEDMAN, EITAN; SHOMRON, NOAM.

In: Genetics Research, 15.05.2017.

Research output: Contribution to journalArticle

EINHORN, YARON ; WEISSGLAS-VOLKOV, DAPHNA ; CARMI, SHAI ; Ostrer, Harry ; FRIEDMAN, EITAN ; SHOMRON, NOAM. / Differential analysis of mutations in the Jewish population and their implications for diseases. In: Genetics Research. 2017.
@article{267505ac4f1340ecb733f91f45885d47,
title = "Differential analysis of mutations in the Jewish population and their implications for diseases",
abstract = "Sequencing large cohorts of ethnically homogeneous individuals yields genetic insights with implications for the entire population rather than a single individual. In order to evaluate the genetic basis of certain diseases encountered at high frequency in the Ashkenazi Jewish population (AJP), as well as to improve variant annotation among the AJP, we examined the entire exome, focusing on specific genes with known clinical implications in 128 Ashkenazi Jews and compared these data to other non-Jewish populations (European, African, South Asian and East Asian). We targeted American College of Medical Genetics incidental finding recommended genes and the Catalogue of Somatic Mutations in Cancer (COSMIC) germline cancer-related genes. We identified previously known disease-causing variants and discovered potentially deleterious variants in known disease-causing genes that are population specific or substantially more prevalent in the AJP, such as in the ATP and HGFAC genes associated with colorectal cancer and pancreatic cancer, respectively. Additionally, we tested the advantage of utilizing the database of the AJP when assigning pathogenicity to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew early-onset breast cancer (BC) patients. Importantly, population-based filtering using our AJP database enabled a reduction in the number of potential causal variants in the BC cohort by 36{\%}. Taken together, population-specific sequencing of the AJP offers valuable, clinically applicable information and improves AJP filter annotation.",
author = "YARON EINHORN and DAPHNA WEISSGLAS-VOLKOV and SHAI CARMI and Harry Ostrer and EITAN FRIEDMAN and NOAM SHOMRON",
year = "2017",
month = "5",
day = "15",
doi = "10.1017/S0016672317000015",
language = "English (US)",
journal = "Genetics Research",
issn = "0016-6723",
publisher = "Cambridge University Press",

}

TY - JOUR

T1 - Differential analysis of mutations in the Jewish population and their implications for diseases

AU - EINHORN, YARON

AU - WEISSGLAS-VOLKOV, DAPHNA

AU - CARMI, SHAI

AU - Ostrer, Harry

AU - FRIEDMAN, EITAN

AU - SHOMRON, NOAM

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Sequencing large cohorts of ethnically homogeneous individuals yields genetic insights with implications for the entire population rather than a single individual. In order to evaluate the genetic basis of certain diseases encountered at high frequency in the Ashkenazi Jewish population (AJP), as well as to improve variant annotation among the AJP, we examined the entire exome, focusing on specific genes with known clinical implications in 128 Ashkenazi Jews and compared these data to other non-Jewish populations (European, African, South Asian and East Asian). We targeted American College of Medical Genetics incidental finding recommended genes and the Catalogue of Somatic Mutations in Cancer (COSMIC) germline cancer-related genes. We identified previously known disease-causing variants and discovered potentially deleterious variants in known disease-causing genes that are population specific or substantially more prevalent in the AJP, such as in the ATP and HGFAC genes associated with colorectal cancer and pancreatic cancer, respectively. Additionally, we tested the advantage of utilizing the database of the AJP when assigning pathogenicity to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew early-onset breast cancer (BC) patients. Importantly, population-based filtering using our AJP database enabled a reduction in the number of potential causal variants in the BC cohort by 36%. Taken together, population-specific sequencing of the AJP offers valuable, clinically applicable information and improves AJP filter annotation.

AB - Sequencing large cohorts of ethnically homogeneous individuals yields genetic insights with implications for the entire population rather than a single individual. In order to evaluate the genetic basis of certain diseases encountered at high frequency in the Ashkenazi Jewish population (AJP), as well as to improve variant annotation among the AJP, we examined the entire exome, focusing on specific genes with known clinical implications in 128 Ashkenazi Jews and compared these data to other non-Jewish populations (European, African, South Asian and East Asian). We targeted American College of Medical Genetics incidental finding recommended genes and the Catalogue of Somatic Mutations in Cancer (COSMIC) germline cancer-related genes. We identified previously known disease-causing variants and discovered potentially deleterious variants in known disease-causing genes that are population specific or substantially more prevalent in the AJP, such as in the ATP and HGFAC genes associated with colorectal cancer and pancreatic cancer, respectively. Additionally, we tested the advantage of utilizing the database of the AJP when assigning pathogenicity to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew early-onset breast cancer (BC) patients. Importantly, population-based filtering using our AJP database enabled a reduction in the number of potential causal variants in the BC cohort by 36%. Taken together, population-specific sequencing of the AJP offers valuable, clinically applicable information and improves AJP filter annotation.

UR - http://www.scopus.com/inward/record.url?scp=85019180389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019180389&partnerID=8YFLogxK

U2 - 10.1017/S0016672317000015

DO - 10.1017/S0016672317000015

M3 - Article

C2 - 28502252

AN - SCOPUS:85019180389

JO - Genetics Research

JF - Genetics Research

SN - 0016-6723

ER -