Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency.
Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency.
复制标题
犬和人近端 Xq 的比较图谱以及犬 X 连锁严重联合免疫缺陷的遗传分析。
DOI：
10.1006/geno.1994.1459
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发表时间：
1994
期刊：
影响因子：
4.4
通讯作者：
Henthorn,PS
中科院分区：
文献类型：
--
作者：
Deschenes,SM;Puck,JM;Dutra,AS;Somberg,RL;Felsburg,PJ;Henthorn,PS
动物和人类遗传疾病的并行遗传分析可以促进致病基因缺陷的识别和表征。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最常见的人类SCID相似。为了获得包含人类中位于近端 Xq、靠近人类 X 连锁 SCID 的基因的犬科动物同线图谱，在犬磷酸甘油酸激酶 (PGK) 和无脉络膜血症 (CHM) 基因座处鉴定了聚 (TG) 多态性。这些加上犬雄激素受体基因 (AR) 外显子 i 中的多态性 Poly(CAG) 序列用于对 X 连锁 SCID 信息的集落成员进行基因分型。未观察到 SCIDX1、AR、PGK 或 CHM 之间的重组。荧光原位杂交将 PGK 和 CHM 定位于狗的 Xq 近端，与人类基因占据的染色体位置相同。体细胞杂交分析和 AR 甲基化差异表明，携带 X 连锁 SCID 的雌性狗与人类携带者具有相同的淋巴细胞限制偏态 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（现已确定为 IL-2 受体的 γ 链）的突变会导致犬和人类 X 连锁 SCID。该方法是比较基因图谱和疾病识别的有效方法。
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 i 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 γ 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.