Bejaoui K, McKenna-Yasek D, Hosler B A, Burns-Deater E, Deater L M, O'Neill G, Haines J L, Brown R H
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Boston, USA.
Neurology. 1999 Feb;52(3):510-5. doi: 10.1212/wnl.52.3.510.
HSN-I is a rare peripheral neuropathy characterized by loss of temperature sensation, ulceration and osteomyelitis of the digits, and subtle distal weakness. A gene for HSN-I has previously been mapped to human chromosome 9q22.1-q22.3 between markers D9S318 and D9S176 in an 8-cM interval in four Australian families.
In a large German-American family with HSN-I, genome-wide linkage analysis was performed on 68 family members extending over five generations and including 17 affected members. Genotyping was performed with PCR, and the resulting genotypes were analyzed with two-point linkage analysis with Fastlink. A YAC contig was constructed based on the Whitehead Institute YAC contig WC9.3.
Two-point linkage analysis resulted in a maximum lod score of 8.2 at theta = 0 for marker D9S1815. Haplotype analysis locates the HSN-I gene between markers D9S1797 and D9S197. Using YAC clones from the Centre d'Etude du Polymorphism Humain YAC Library, we constructed a YAC contig spanning these markers. Based on the radiation hybrid map of the human genome, we estimate that the size of this interval is less than 2,500 kb.
Our study confirms linkage of a putative HSN-I gene to chromosome 9q22, considerably narrows the HSN-I locus, and provides a basis for identification of the HSN-I gene.
1）在一个源自德国的美国家庭中，证实遗传性感觉神经病1型（HSN-I）与人类9号染色体q22区域的连锁关系。2）构建跨越HSN-I候选区间的酵母人工染色体（YAC）重叠群。3）研究HSN-I重叠群中潜在的候选基因。
HSN-I是一种罕见的周围神经病，其特征为温度觉丧失、手指溃疡和骨髓炎，以及轻微的远端肌无力。先前在四个澳大利亚家庭中，已将HSN-I基因定位到9号染色体q22.1-q22.3区域，位于标记D9S318和D9S176之间，间隔为8厘摩。
在一个患有HSN-I的德裔美国家庭中，对68名家庭成员进行了全基因组连锁分析，这些成员跨越五代，包括17名患病成员。采用聚合酶链反应（PCR）进行基因分型，并使用Fastlink软件通过两点连锁分析对所得基因型进行分析。基于怀特黑德研究所的YAC重叠群WC9.3构建YAC重叠群。
两点连锁分析显示，标记D9S1815在θ=0时的最大对数优势得分为8.2。单倍型分析将HSN-I基因定位在标记D9S1797和D9S197之间。利用来自人类多态性研究中心YAC文库的YAC克隆，我们构建了跨越这些标记的YAC重叠群。根据人类基因组的辐射杂种图谱，我们估计该区间的大小小于2500 kb。
我们的研究证实了一个假定的HSN-I基因与9号染色体q22区域的连锁关系，显著缩小了HSN-I基因座的范围，并为鉴定HSN-I基因提供了基础。
