HUMAN BIOCHEMICAL GENETICS

1.该科成员已创建了一种部分细菌人造 猪胱氨酸病基因临界区的染色体重叠群 染色体17p。他们已经绘制了超过25个序列标签位点和 这一区域有几个候选基因。完整的重叠群将是 样本测序及其表达序列标签的偶然性， 通过与数据库的序列比较来鉴定，将被检查。 然后将对这些候选基因进行测试，以确定哪个是该基因 在胱氨酸病方面有缺陷。2.一个与人的基因同源的人基因 流感嗜血杆菌UDP-N-乙酰氨基葡萄糖2-差向异构酶基因已被 与世隔绝。这种基因可能在唾液酸尿症中发生突变，这是一种由于 CMP唾液酸对差向异构体酶的反馈缺陷抑制。3.A 患有MAT I/III缺陷的43岁男子被发现为纯合子 在MAT1A基因中插入了539TG。他的正常神经学检查 核磁共振显示MAT1A基因产物的截断，通过预测 他的突变并不一定会导致大脑脱髓鞘，因为 其他调查人员的建议。4.49名患者 Hermansky-Pudlak综合征在NIH临床中心进行检查。这个 波多黎各典型的HPS基因16个碱基重复的25个纯合子 Rican患者的肺部限制性疾病比24例缺乏的患者更多 这种突变。此外，有记录的两名波多黎各患者 HPS被证明缺少16个碱基的重复，并具有完全 正常的HPS基因序列。这表明HPS基因座具有异质性。

1. Members of the Section have created a partial bacterial artificial chromosome contig across the critical region of the cystinosis gene on chromosome 17p. They have mapped more than 25 sequence tagged sites and several candidate genes to this region. The complete contig will be sample sequenced and its contingent of expressed sequence tags, identified by sequence comparison with databanks, will be examined. These candidate genes will then be tested to determine which is the gene defective in cystinosis. 2. A human cDNA with homology to the Haemophilus influenza UDP-N-Acetylglucosamine 2-epimerase gene has been isolated. This gene is presumably mutated in sialuria, a disorder due to defective feedback inhibition of the epimerase by CMP sialic acid. 3. A 43-year old man with MAT I/III deficiency was found to be homozygous for a 539TG insertion in the MAT1A gene. His normal neurological examination and MRI indicates that truncation of the MAT1A gene product, predicted by his mutation, does not necessarily result in brain demyelination, as suggested by other investigators. 4. Forty-nine patients with Hermansky-Pudlak syndrome were examined at the NIH Clinical Center. The 25 homozygous for a 16-bp duplication in the HPS gene typical of Puerto Rican patients had more pulmonary restrictive disease than the 24 lacking this mutation. In addition, two Puerto Rican patients with documented HPS were shown to lack the 16-bp duplication and to have an entirely normal HPS gene sequence. This indicates locus heterogeneity for HPS.