家族性自主神经功能异常基因在9号染色体上的定位及用于基因诊断的DNA标记的确定。

Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis.

作者信息

Blumenfeld A, Slaugenhaupt S A, Axelrod F B, Lucente D E, Maayan C, Liebert C B, Ozelius L J, Trofatter J A, Haines J L, Breakefield X O

机构信息

Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston 02129.

出版信息

Nat Genet. 1993 Jun;4(2):160-4. doi: 10.1038/ng0693-160.

DOI:10.1038/ng0693-160

PMID:8102296

Abstract

Familial dysautonomia (DYS), the Riley-Day syndrome, is an autosomal recessive disorder characterized by developmental loss of neurons from the sensory and autonomic nervous system. It is limited to the Ashkenazi Jewish population, where the carrier frequency is 1 in 30. We have mapped the DYS gene to chromosome 9q31-q33 by linkage with ten DNA markers in 26 families. The maximum lod score of 21.1 with no recombinants was achieved with D9S58. This marker also showed strong linkage disequilibrium with DYS, with one allele present on 73% of affected chromosomes compared to 5.4% of controls (chi 2 = 3142, 15 d.f. p < 0.0001). D9S53 and D9S105 represent the closest flanking markers for the disease gene. This localization will permit prenatal diagnosis of DYS in affected families and aid the isolation of the disease gene.

摘要

家族性自主神经功能异常（DYS），即赖利-戴综合征，是一种常染色体隐性疾病，其特征为感觉和自主神经系统的神经元在发育过程中丧失。该病仅限于阿什肯纳兹犹太人群体，携带者频率为1/30。我们通过在26个家族中与10个DNA标记进行连锁分析，将DYS基因定位到了9号染色体的q31-q33区域。与D9S58连锁时获得了最大对数优势分数21.1，且无重组现象。该标记还显示出与DYS存在强烈的连锁不平衡，在73%的患病染色体上存在一个等位基因，而在对照染色体上这一比例为5.4%（卡方检验：χ2 = 3142，自由度15，p < 0.0001）。D9S53和D9S105是该疾病基因最接近的侧翼标记。这一定位将有助于对患病家族进行DYS的产前诊断，并有助于分离该疾病基因。