Hoehe M R, Ehrenreich H, Otterud B, Caenazzo L, Plaetke R, Zander H, Leppert M
Clinical Neurogenetics Branch, NIMH, NIH, Bethesda, MD 20892.
Cytogenet Cell Genet. 1993;62(2-3):131-5. doi: 10.1159/000133455.
We determined the precise genetic location of the human endothelin-1 gene (EDN1), which encodes a peptide with extremely potent vasoactive properties and is apparently involved in a spectrum of diseases ranging from hypertension to asthma. Analyzing the segregation of a four-allele EDN1 polymorphism in 40 CEPH families including 480 individuals, we detected significant linkage of EDN1 to DNA markers spanning the telomeric half of chromosome arm 6p. EDN1 was closest to the highly polymorphic nucleotide-repeat marker D6S89 at a theta = 0.06 with the highest pairwise LOD score Zmax = 31.2. Subsequent multipoint analysis placed EDN1 at 8 cM distal to D6S89; EDN1 was flanked at its telomeric site at a 13-cM distance by the gene encoding the A subunit of blood clotting factor XIII (F13A1). Furthermore, EDN1 was located at approximately 34-36 cM distal to the HLA region defined by HLA-A, -B, and -DRB1, and 31 cM proximal to the most telomeric marker D6S7. This location of EDN1 on the primary genetic map is strongly supported with odds of 2.7 x 10(12):1 against the next best alternative.
我们确定了人类内皮素 -1 基因（EDN1）的精确基因定位，该基因编码一种具有极强血管活性特性的肽，显然参与了从高血压到哮喘等一系列疾病的发生发展。通过分析包括 480 名个体的 40 个 CEPH 家系中四等位基因 EDN1 多态性的分离情况，我们检测到 EDN1 与跨越 6 号染色体短臂端粒半段的 DNA 标记存在显著连锁。EDN1 与高度多态性的核苷酸重复标记 D6S89 距离最近，θ = 0.06，最高双点连锁值 Zmax = 31.2。随后的多点分析将 EDN1 定位在 D6S89 远端 8 cM 处；在其端粒位点，EDN1 与凝血因子 XIII A 亚基（F13A1）编码基因相距 13 cM。此外，EDN1 位于由 HLA -A、-B 和 -DRB1 定义的 HLA 区域远端约 34 - 36 cM 处，以及最末端标记 D6S7 近端 31 cM 处。EDN1 在主要遗传图谱上的这一位置得到了有力支持，与次优替代位置相比，其优势比为 2.7×10¹²:1。
