Deschênes S M, Puck J M, Dutra A S, Somberg R L, Felsburg P J, Henthorn P S
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia.
Genomics. 1994 Sep 1;23(1):62-8. doi: 10.1006/geno.1994.1459.
Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly(TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly(CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the gamma chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification.
对动物和人类遗传疾病进行平行遗传分析有助于识别和表征致病基因缺陷。例如，犬X连锁严重联合免疫缺陷（SCID）的临床、病理和免疫学表现与人类最常见的SCID形式相似。为了构建一个犬类同线基因图谱，包括在人类中位于近端Xq、靠近人类X连锁SCID的基因，在犬磷酸甘油酸激酶（PGK）和脉络膜血色素沉着症（CHM）基因座处鉴定了多聚（TG）多态性。这些多态性加上犬雄激素受体基因（AR）外显子1中的多态性多聚（CAG）序列，被用于对X连锁SCID信息丰富的群体成员进行基因分型。在SCIDX1、AR、PGK或CHM之间未观察到重组。荧光原位杂交将PGK和CHM定位到犬的近端Xq，与人类基因在相同的染色体位置。体细胞杂交分析和AR处的甲基化差异表明，携带X连锁SCID的雌性犬具有与人类携带者相同的淋巴细胞受限的偏态X染色体失活模式。这些遗传和表型发现提供了证据，表明同一基因（现被鉴定为IL-2受体的γ链）中的突变导致犬类和人类X连锁SCID。这种方法是比较基因图谱绘制和疾病识别的有效方法。
