HUMAN BIOCHEMICAL GENETICS

该科成员已将胱氨酸病基因定位到染色体上， 17p，现在已经将该基因的区域缩小到130 kb的跨度， 鉴定新的多态性标记和信息重组体。 几个非多态性标记已被定位到该地区的辐射 混合分析 两个P1克隆跨越胱氨酸病基因区，侧翼为 标记为D17S1828和D17S2167。 由于它们重叠， 基因必须位于其中一个克隆上。 确定和 对候选基因的测试仍在继续。 我们已经鉴定了24种rab蛋白（小的单体GTP结合蛋白）， 蛋白质）。 Rab30是一种新的203个氨基酸残基的蛋白质， rab22b似乎是人的同源物的同种型， 犬科兔子22. 此外，包含rab的rab 27 a和rab 27 b也可以是 在黑素细胞和血小板中表达的亚家族，是 参与人类和小鼠色素稀释和 血小板储存池缺陷。 酪氨酸转运系统的特征在于黑素体中的 鼠黑素细胞。 它表现出反向传输和饱和性， 酪氨酸的表观Km为54 μ M。 在其基底偏好中， 它类似于大鼠甲状腺FRTL-5细胞的溶酶体系统h。 的 黑素细胞的黑素体运输系统似乎对黑素细胞的生长至关重要。 黑色素的产生。 该科检查了30多名赫尔曼斯基-普德拉克综合征患者， 一种由白化病、出血素质和溶酶体组成的疾病 蜡样脂褐质的贮存。 一半的病人是波多黎各人。 Dolichol已被鉴定为蜡样脂褐质的组分， 一些患者表现出胆固醇水平升高， 辅酶Q10，都表明参与胆固醇合成 在这种混乱中。 该疾病的临床特征可能 指向治疗的途径

Members of the Section, having mapped the cystinosis gene to chromosome 17p, have now narrowed the region of the gene to a 130 kb span by identifying new polymorphic markers and informative recombinants. Several nonpolymorphic markers have been mapped to the area by radiation hybrid analysis. Two P1 clones span the cystinosis gene region, flanked by markers D17S1828 and D17S2167. Since they overlap, the cystinosis gene must be located on one of the clones. The identification and testing of candidate genes continues. We have identified 24 rab proteins (small, monomeric GTP-binding proteins) in melanocytes. Rab30 represents a novel protein of 203 amino acids, and rab22b appears to be an isoform of the human homologue of canine rab22. Furthermore, rab27a and rab27b, which comprise a rab subfamily expressed in both melanocytes and platelets, are candidates for involvement in human and mouse disorders of pigment dilution and a platelet storage pool defect. A tyrosine transport system has been characterized in the melanosomes of murine melanocytes. It exhibits countertransport and saturability, with an apparent Km for tyrosine of 54 microM. In its substrate preferences, it resembles lysosomal system h of rat thyroid FRTL-5 cells. The melanocyte's melanosomal transport system appears critical for the production of the pigment melanin. The Section has examined over 30 patients with Hermansky-Pudlak syndrome, a disorder consisting of albinism, a bleeding diathesis, and lysosomal storage of ceroid lipofuscin. Half the patients have been Puerto Rican. Dolichols have been identified as components of the ceroid lipofuscin and several patients have exhibited increased levels of cholesterol and coenzyme Q10, all suggesting involvemnt of the cholesterol synthetic pathway in this disorder. Clinical characterization of the disease may point to avenues of therapy.