Carrier frequency analysis of mutations causing autosomal-recessive-inherited retinal diseases in the Israeli population
Inherited retinal diseases (IRDs) are heterogeneous phenotypes caused by variants in a large number of genes. Disease prevalence and the frequency of carriers in the general population have been estimated in only a few studies, but are largely unknown. To this end, we developed two parallel methods...
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| Veröffentlicht in: | European journal of human genetics : EJHG 2018-08, Vol.26 (8), p.1159-1166 |
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| creator | Hanany, Mor Allon, Gilad Kimchi, Adva Blumenfeld, Anat Newman, Hadas Pras, Eran Wormser, Ohad S Birk, Ohad Gradstein, Libe Banin, Eyal Ben-Yosef, Tamar Sharon, Dror |
| description | Inherited retinal diseases (IRDs) are heterogeneous phenotypes caused by variants in a large number of genes. Disease prevalence and the frequency of carriers in the general population have been estimated in only a few studies, but are largely unknown. To this end, we developed two parallel methods to calculate carrier frequency for mutations causing autosomal-recessive (AR) IRDs in the Israeli population. We created an SQL database containing information on 178 genes from gnomAD (including genotyping of 5706 Ashkenazi Jewish (AJ) individuals) and our cohort of >2000 families with IRDs. Carrier frequency for IRD variants and genes was calculated based on allele frequency values and the Hardy-Weinberg (HW) equation. We identified 399 IRD-causing variants in 111 genes in Israeli patients and AJ controls. For the AJ subpopulation, gnomAD and HW-based regression analysis showed high correlation, therefore allowing one to use HW-based data as a reliable estimate of carrier frequency. Overall, carrier frequency per subpopulation ranges from 1/2.2 to 1/9.6 individuals, with the highest value obtained for the Arab-Muslim subpopulation in Jerusalem reaching an extremely high carrier rate of 44.7%. Carrier frequency per gene ranges from 1/31 to 1/11994 individuals. We estimate the total carrier frequency for AR-IRD mutations in the Israeli population as over 30%, a relatively high carrier frequency with marked variability among subpopulations. Therefore, these data are highly important for more reliable genetic counseling and genetic screening. Our method can be adapted to study other populations, either based on allele frequency data or cohort of patients. |
| doi_str_mv | 10.1038/s41431-018-0152-0 |
| format | Article |
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Disease prevalence and the frequency of carriers in the general population have been estimated in only a few studies, but are largely unknown. To this end, we developed two parallel methods to calculate carrier frequency for mutations causing autosomal-recessive (AR) IRDs in the Israeli population. We created an SQL database containing information on 178 genes from gnomAD (including genotyping of 5706 Ashkenazi Jewish (AJ) individuals) and our cohort of >2000 families with IRDs. Carrier frequency for IRD variants and genes was calculated based on allele frequency values and the Hardy-Weinberg (HW) equation. We identified 399 IRD-causing variants in 111 genes in Israeli patients and AJ controls. For the AJ subpopulation, gnomAD and HW-based regression analysis showed high correlation, therefore allowing one to use HW-based data as a reliable estimate of carrier frequency. Overall, carrier frequency per subpopulation ranges from 1/2.2 to 1/9.6 individuals, with the highest value obtained for the Arab-Muslim subpopulation in Jerusalem reaching an extremely high carrier rate of 44.7%. Carrier frequency per gene ranges from 1/31 to 1/11994 individuals. We estimate the total carrier frequency for AR-IRD mutations in the Israeli population as over 30%, a relatively high carrier frequency with marked variability among subpopulations. Therefore, these data are highly important for more reliable genetic counseling and genetic screening. Our method can be adapted to study other populations, either based on allele frequency data or cohort of patients.</description><identifier>ISSN: 1018-4813</identifier><identifier>EISSN: 1476-5438</identifier><identifier>DOI: 10.1038/s41431-018-0152-0</identifier><identifier>PMID: 29706639</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Alleles ; Arabs - genetics ; Eye Diseases, Hereditary - genetics ; Gene Frequency ; Genes, Recessive ; Genetic counseling ; Genetic screening ; Genotyping ; Heterozygote ; Humans ; Israel ; Jews - genetics ; Mutation ; Population ; Population - genetics ; Population studies ; Retina ; Subpopulations</subject><ispartof>European journal of human genetics : EJHG, 2018-08, Vol.26 (8), p.1159-1166</ispartof><rights>Copyright Nature Publishing Group Aug 2018</rights><rights>European Society of Human Genetics 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-36cbefce5413c3e993e4c8613dd98b5c73ef61b2af6b92944dbc29587208c4b23</citedby><cites>FETCH-LOGICAL-c427t-36cbefce5413c3e993e4c8613dd98b5c73ef61b2af6b92944dbc29587208c4b23</cites><orcidid>0000-0002-8203-2721</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057931/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057931/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29706639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanany, Mor</creatorcontrib><creatorcontrib>Allon, Gilad</creatorcontrib><creatorcontrib>Kimchi, Adva</creatorcontrib><creatorcontrib>Blumenfeld, Anat</creatorcontrib><creatorcontrib>Newman, Hadas</creatorcontrib><creatorcontrib>Pras, Eran</creatorcontrib><creatorcontrib>Wormser, Ohad</creatorcontrib><creatorcontrib>S Birk, Ohad</creatorcontrib><creatorcontrib>Gradstein, Libe</creatorcontrib><creatorcontrib>Banin, Eyal</creatorcontrib><creatorcontrib>Ben-Yosef, Tamar</creatorcontrib><creatorcontrib>Sharon, Dror</creatorcontrib><title>Carrier frequency analysis of mutations causing autosomal-recessive-inherited retinal diseases in the Israeli population</title><title>European journal of human genetics : EJHG</title><addtitle>Eur J Hum Genet</addtitle><description>Inherited retinal diseases (IRDs) are heterogeneous phenotypes caused by variants in a large number of genes. Disease prevalence and the frequency of carriers in the general population have been estimated in only a few studies, but are largely unknown. To this end, we developed two parallel methods to calculate carrier frequency for mutations causing autosomal-recessive (AR) IRDs in the Israeli population. We created an SQL database containing information on 178 genes from gnomAD (including genotyping of 5706 Ashkenazi Jewish (AJ) individuals) and our cohort of >2000 families with IRDs. Carrier frequency for IRD variants and genes was calculated based on allele frequency values and the Hardy-Weinberg (HW) equation. We identified 399 IRD-causing variants in 111 genes in Israeli patients and AJ controls. For the AJ subpopulation, gnomAD and HW-based regression analysis showed high correlation, therefore allowing one to use HW-based data as a reliable estimate of carrier frequency. Overall, carrier frequency per subpopulation ranges from 1/2.2 to 1/9.6 individuals, with the highest value obtained for the Arab-Muslim subpopulation in Jerusalem reaching an extremely high carrier rate of 44.7%. Carrier frequency per gene ranges from 1/31 to 1/11994 individuals. We estimate the total carrier frequency for AR-IRD mutations in the Israeli population as over 30%, a relatively high carrier frequency with marked variability among subpopulations. Therefore, these data are highly important for more reliable genetic counseling and genetic screening. Our method can be adapted to study other populations, either based on allele frequency data or cohort of patients.</description><subject>Alleles</subject><subject>Arabs - genetics</subject><subject>Eye Diseases, Hereditary - genetics</subject><subject>Gene Frequency</subject><subject>Genes, Recessive</subject><subject>Genetic counseling</subject><subject>Genetic screening</subject><subject>Genotyping</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Israel</subject><subject>Jews - genetics</subject><subject>Mutation</subject><subject>Population</subject><subject>Population - genetics</subject><subject>Population studies</subject><subject>Retina</subject><subject>Subpopulations</subject><issn>1018-4813</issn><issn>1476-5438</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkU1rFTEUhoMotlZ_gBsJuHEzmq-ZSTaCXNQWCm50HTKZM70pM8k1J1O8_96MtxbrIiTwfiQ5DyGvOXvPmdQfUHElecO4rqsVDXtCzrnqu6ZVUj-t501Rmssz8gLxlrEq9vw5OROmZ10nzTn5tXM5B8h0yvBzheiP1EU3HzEgTRNd1uJKSBGpdyuGeEPdWhKmxc1NBg-I4Q6aEPeQQ4GRZiihxukYEBwC0hBp2QO9wuxgDvSQDuv8p_EleTa5GeHV_X5Bfnz5_H132Vx_-3q1-3TdeCX60sjODzB5aBWXXoIxEpTXHZfjaPTQ-l7C1PFBuKkbjDBKjYMXptW9YNqrQcgL8vHUe1iHBUYPsWQ320MOi8tHm1ywj5UY9vYm3dmOtb2RvBa8uy_IqU4Ii10CephnFyGtaAWTQjMh1XbX2_-st2nNdR6bq29boTomq4ufXD4nxAzTw2M4sxtXe-JqKz27cbWsZt78-4uHxF-Q8jcTr6HL</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Hanany, Mor</creator><creator>Allon, Gilad</creator><creator>Kimchi, Adva</creator><creator>Blumenfeld, Anat</creator><creator>Newman, Hadas</creator><creator>Pras, Eran</creator><creator>Wormser, Ohad</creator><creator>S Birk, Ohad</creator><creator>Gradstein, Libe</creator><creator>Banin, Eyal</creator><creator>Ben-Yosef, Tamar</creator><creator>Sharon, Dror</creator><general>Nature Publishing Group</general><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8203-2721</orcidid></search><sort><creationdate>20180801</creationdate><title>Carrier frequency analysis of mutations causing autosomal-recessive-inherited retinal diseases in the Israeli population</title><author>Hanany, Mor ; 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Disease prevalence and the frequency of carriers in the general population have been estimated in only a few studies, but are largely unknown. To this end, we developed two parallel methods to calculate carrier frequency for mutations causing autosomal-recessive (AR) IRDs in the Israeli population. We created an SQL database containing information on 178 genes from gnomAD (including genotyping of 5706 Ashkenazi Jewish (AJ) individuals) and our cohort of >2000 families with IRDs. Carrier frequency for IRD variants and genes was calculated based on allele frequency values and the Hardy-Weinberg (HW) equation. We identified 399 IRD-causing variants in 111 genes in Israeli patients and AJ controls. For the AJ subpopulation, gnomAD and HW-based regression analysis showed high correlation, therefore allowing one to use HW-based data as a reliable estimate of carrier frequency. Overall, carrier frequency per subpopulation ranges from 1/2.2 to 1/9.6 individuals, with the highest value obtained for the Arab-Muslim subpopulation in Jerusalem reaching an extremely high carrier rate of 44.7%. Carrier frequency per gene ranges from 1/31 to 1/11994 individuals. We estimate the total carrier frequency for AR-IRD mutations in the Israeli population as over 30%, a relatively high carrier frequency with marked variability among subpopulations. Therefore, these data are highly important for more reliable genetic counseling and genetic screening. Our method can be adapted to study other populations, either based on allele frequency data or cohort of patients.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>29706639</pmid><doi>10.1038/s41431-018-0152-0</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-8203-2721</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Alleles Arabs - genetics Eye Diseases, Hereditary - genetics Gene Frequency Genes, Recessive Genetic counseling Genetic screening Genotyping Heterozygote Humans Israel Jews - genetics Mutation Population Population - genetics Population studies Retina Subpopulations |
| title | Carrier frequency analysis of mutations causing autosomal-recessive-inherited retinal diseases in the Israeli population |
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