Gene selection for the Australian Reproductive Genetic Carrier Screening Project ("Mackenzie's Mission")
Gene selection for the Australian Reproductive Genetic Carrier Screening Project ("Mackenzie's Mission")
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DOI：
10.1038/s41431-020-0685-x
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发表时间：
2020-07-16
影响因子：
5.2
通讯作者：
Delatycki, Martin B.
中科院分区：
文献类型：
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作者：
Kirk, Edwin P.;Ong, Royston;Delatycki, Martin B.
生殖遗传携带者筛查的目的是为夫妇提供关于他们生育具有某些常染色体隐性遗传和X连锁遗传条件的孩子的机会的信息。我们开发了一个基因列表，用于“麦肯齐的使命”，一个研究项目，其中10,000对夫妇将接受筛选。选择基因的标准是：这种疾病应该是限制生命或致残的，在儿童期发病，这样夫妇就可能采取措施避免生一个受影响的孩子;和/或早期诊断和干预将大大改变结果。需要强有力的证据证明基因-表型关系。候选基因从OMIM中鉴定，并通过审查23个商业和公开的基因列表。基因由16名临床遗传学家使用标准操作程序进行审查，该过程由一个多学科委员会监督，该委员会包括临床遗传学家，遗传咨询师，伦理学家，患有遗传疾病的儿童的父母以及来自诊断和研究背景的科学家。1300个基因符合标准。与非综合征性耳聋和非综合征性性别发育差异相关的基因未包括在内。我们的经验强调，基因选择的载体筛选小组需要一个动态的过程，不断审查和完善。
Reproductive genetic carrier screening aims to offer couples information about their chance of having children with certain autosomal recessive and X-linked genetic conditions. We developed a gene list for use in "Mackenzie's Mission", a research project in which 10,000 couples will undergo screening. Criteria for selecting genes were: the condition should be life-limiting or disabling, with childhood onset, such that couples would be likely to take steps to avoid having an affected child; and/or be one for which early diagnosis and intervention would substantially change outcome. Strong evidence for gene-phenotype relationship was required. Candidate genes were identified from OMIM and via review of 23 commercial and published gene lists. Genes were reviewed by 16 clinical geneticists using a standard operating procedure, in a process overseen by a multidisciplinary committee which included clinical geneticists, genetic counselors, an ethicist, a parent of a child with a genetic condition and scientists from diagnostic and research backgrounds. 1300 genes met criteria. Genes associated with non-syndromic deafness and non-syndromic differences of sex development were not included. Our experience has highlighted that gene selection for a carrier screening panel needs to be a dynamic process with ongoing review and refinement.