Linkage analysis between the major histocompatibility system and insulin-dependent diabetes in families with patients in two consecutive generations.
Linkage analysis between the major histocompatibility system and insulin-dependent diabetes in families with patients in two consecutive generations.
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连续两代患者家族中主要组织相容性系统与胰岛素依赖型糖尿病的关联分析。
DOI：
10.1172/jci109704
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
L. Greenberg
中科院分区：
文献类型：
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作者：
J. Barbosa;M. Chern;V. Anderson;H. Noreen;S. Johnson;N. Reinsmoen;R. Mccarty;R. King;L. Greenberg
我们有组织相容性（HLA）基因分型28个家庭与胰岛素依赖型糖尿病患者在两个或两个以上的连续世代，通常父母和孩子。这种确定策略用于最大限度地提高在一个家族中获得同种类型疾病和常染色体显性遗传模式的可能性。对76例糖尿病患者和169例非糖尿病患者进行了研究。糖尿病患者Dw 3、Dw 4抗原和Dw 3/Dw 4基因型频率分别为59%、68%和30%，而正常对照组分别为15%、12%和2%，糖尿病患者非糖尿病亲属分别为43%、41%和10%。dw 2是目前在只有一个糖尿病患者（4%），与18%的正常对照和17%的nondiabetic relationships.HLA单倍型一致性进行了分析，同胞对有关的单倍型共享的受影响的父母/子女对，和糖尿病同胞对在每个同胞。结果未能揭示预期HLA单倍型配型的偏差。假设一个常染色体显性遗传模式和几个等位基因水平，HLA和糖尿病之间的连锁分析进行。在50%重复率下，重组分数为0.29，总lod得分为0.37。尽管连锁和一致性分析结果尚无定论，但它们似乎与我们报告的父母正常且有两个或更多糖尿病同胞的家庭的结果不同。由于确定偏差可能以无法量化的方式影响了这些结果，因此尚不确定这两种类型的家庭在遗传上是否不同。然而，显着差异的lod得分的50%外显常染色体隐性遗传模型之间的两种类型的家庭是兼容的遗传相异。然而，高频率的Dw 3和Dw 4抗原，Dw 3/Dw 4基因型，和Dw 2的频率下降，表明存在两个或两个以上的重要的糖尿病遗传因素与D区域的HLA在这些家庭。
We have histocompatibility (HLA) genotyped 28 families with insulin-dependent diabetics in two or more consecutive generations, usually parent and child. This strategy of ascertainment was used to maximize the likelihood of obtaining a homogeneous type of disease within a family, and an autosomal dominant mode of inheritance. 76 diabetics and 169 nondiabetics were studied in these families. The frequencies of the antigens Dw3 and Dw4, and the genotype Dw3/Dw4 among the diabetics are 59, 68, and 30%, respectively, as compared with 15, 12, and 2% in normal controls, and 43, 41, and 10% in the nondiabetic relatives of the diabetics. Dw2 is present in only one diabetic (4%), as compared with 18% in normal controls and 17% in nondiabetic relatives.HLA haplotype concordance was analyzed for sib pairs in relation to the haplotype shared by the affected parent/child pair, and for the diabetic sib pairs within each sibship. The results failed to reveal deviations in the expected HLA haplotype assortment. Assuming an autosomal dominant mode and several penetrance levels, linkage analysis between the HLA and diabetes was performed. The total lod score is 0.37 for a recombination fraction of 0.29 at 50% penetrance. Although the linkage and concordance analysis results are inconclusive, they seem to be different from those reported by us for families with normal parents and two or more diabetic sibs. Because ascertainment biases may have influenced these results in an unquantifiable manner, it is not certain whether the two types of families are genetically different. However, the marked difference in the lod scores for the 50% penetrant autosomal recessive model between the two types of families is compatible with a genetic dissimilarity between them. The high frequency of the Dw3 and Dw4 antigens, the Dw3/Dw4 genotype, and the decreased frequency of Dw2, however, indicate the existence of two or more important diabetic genetic factors associated with the D region of the HLA in these families.