Cargando…
Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel
Carrier screening for autosomal recessive variants has become a cornerstone of community and public health genetics. While the first carrier screening programs were confined to conditions with relatively high prevalence, and hence well-known carrier frequency, the number of candidate genes has incre...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314508/ https://www.ncbi.nlm.nih.gov/pubmed/35661981 http://dx.doi.org/10.1007/s12687-022-00593-0 |
_version_ | 1784754334484922368 |
---|---|
author | Schmidtke, Jörg Krawczak, Michael |
author_facet | Schmidtke, Jörg Krawczak, Michael |
author_sort | Schmidtke, Jörg |
collection | PubMed |
description | Carrier screening for autosomal recessive variants has become a cornerstone of community and public health genetics. While the first carrier screening programs were confined to conditions with relatively high prevalence, and hence well-known carrier frequency, the number of candidate genes has increased greatly since the advent of high-throughput DNA sequencing technologies. The epidemiological database of the ensuing gene panels is mostly sparse, and judgement of their performance is, therefore, anything but straightforward. We therefore derived estimates of the carrier detection probabilities among non-consanguineous and consanguineous couples as expected using the ‘Tier 3’ carrier screening gene panel recently recommended by the American College of Medical Genetics (ACMG). For non-Finnish Europeans, the respective estimate for unrelated couples equals 0.63%, implying that the ACMG Tier 3 panel accounts for over 90% of the genetic load for autosomal recessive diseases in this population. Among the offspring of first cousins, the corresponding incidence is expected to be tenfold higher, an increase still consistent with previous estimates of the overall risk of birth defects for this type of mating. Our considerations are intended to aid the implementation of carrier screening programs and to provide additional support to reproductive counselling and to obtaining informed consent. |
format | Online Article Text |
id | pubmed-9314508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-93145082022-07-27 Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel Schmidtke, Jörg Krawczak, Michael J Community Genet Original Article Carrier screening for autosomal recessive variants has become a cornerstone of community and public health genetics. While the first carrier screening programs were confined to conditions with relatively high prevalence, and hence well-known carrier frequency, the number of candidate genes has increased greatly since the advent of high-throughput DNA sequencing technologies. The epidemiological database of the ensuing gene panels is mostly sparse, and judgement of their performance is, therefore, anything but straightforward. We therefore derived estimates of the carrier detection probabilities among non-consanguineous and consanguineous couples as expected using the ‘Tier 3’ carrier screening gene panel recently recommended by the American College of Medical Genetics (ACMG). For non-Finnish Europeans, the respective estimate for unrelated couples equals 0.63%, implying that the ACMG Tier 3 panel accounts for over 90% of the genetic load for autosomal recessive diseases in this population. Among the offspring of first cousins, the corresponding incidence is expected to be tenfold higher, an increase still consistent with previous estimates of the overall risk of birth defects for this type of mating. Our considerations are intended to aid the implementation of carrier screening programs and to provide additional support to reproductive counselling and to obtaining informed consent. Springer Berlin Heidelberg 2022-06-04 2022-08 /pmc/articles/PMC9314508/ /pubmed/35661981 http://dx.doi.org/10.1007/s12687-022-00593-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Schmidtke, Jörg Krawczak, Michael Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel |
title | Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel |
title_full | Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel |
title_fullStr | Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel |
title_full_unstemmed | Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel |
title_short | Carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the ACMG ‘Tier 3’ panel |
title_sort | carrier detection probabilities for autosomal recessive variants in unrelated and consanguineous couples — an evaluation of the 86 genes of the acmg ‘tier 3’ panel |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314508/ https://www.ncbi.nlm.nih.gov/pubmed/35661981 http://dx.doi.org/10.1007/s12687-022-00593-0 |
work_keys_str_mv | AT schmidtkejorg carrierdetectionprobabilitiesforautosomalrecessivevariantsinunrelatedandconsanguineouscouplesanevaluationofthe86genesoftheacmgtier3panel AT krawczakmichael carrierdetectionprobabilitiesforautosomalrecessivevariantsinunrelatedandconsanguineouscouplesanevaluationofthe86genesoftheacmgtier3panel |