A comprehensive search for segregation distortion in HLA

Klitz, William; Lo, Sing Kai; Neugebauer, M.; Baur, Max P.; Albert, E. D.; Thomson, Glenys

doi:10.1016/0198-8859(87)90013-9

Cited by 30 publications

(23 citation statements)

References 27 publications

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“…This unexpected finding was probably due to chance variation, but needs to be verified in other healthy families. Despite this we did not observe any distortion in segregation ratios in the control families which is consistent with previous reports [29,[38][39][40][41]. The only haplotype inherited more frequently than expected, was C2 -B18 -DR2 [39].…”

Section: Discussionsupporting

confidence: 80%

“…Despite this we did not observe any distortion in segregation ratios in the control families which is consistent with previous reports [29,[38][39][40][41]. The only haplotype inherited more frequently than expected, was C2 -B18 -DR2 [39]. There were no significant differences in transmission rates from mother or father [29,[38][39][40][41].…”

Section: Discussionsupporting

confidence: 79%

“…The only haplotype inherited more frequently than expected, was C2 -B18 -DR2 [39]. There were no significant differences in transmission rates from mother or father [29,[38][39][40][41]. Hence, there does not seem to be a segregation distortion in families without IDDM.…”

Section: Discussionmentioning

confidence: 82%

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Inheritance of MHC class II genes in IDDM studied in population-based affected and control families

et al. 1994

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SummaryThe transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p < 0.025) and DQBI*0302 (p < 0.01) from both parents to the index patient. There was an increased transmission of DQBI*0302 (p < 0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p < 0.01) of positively associated haplotypes (DR4-DQAI* 0301-DQBl*0302, DR3-DQAI*0501-DQBI*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development. [Diabetologia (1994[Diabetologia ( ) 37: 1105[Diabetologia ( -1112

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 79%

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Inheritance of MHC class II genes in IDDM studied in population-based affected and control families

et al. 1994

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“…Comparison to the results of other studies, like Klitz et al [7] and Jin et al [6], does not reveal consistent patterns of HLA allele transmission. In our data set, paternal A26 was transmitted less often than expected, whereas in the Caucasian population sample of Klitz et al [7] it was transmitted at a higher than 50% frequency.…”

Section: Discussionmentioning

confidence: 70%

“…Most studies in this field have been conducted using small samples of subjects ascertained through an HLA-associated disease, like IDDM, which makes the interpretation of the results difficult and is also a potential source of bias. To our knowledge, there are only two studies using random samples from nondiseased populations [6,7]; however, the data were collected from several populations around the world (International Histocompatibility Workshop data [19]), and thus transmission distortion could be found only if it existed simultaneously in several populations. Neither of the studies mentioned above found evidence of significant transmission distortion.…”

Section: Introductionmentioning

confidence: 99%

Estimation of Transmission Probabilities in Families Ascertained through a Proband with Variable Age-at-Onset Disease: Application to the HLA A, B and DR Loci in Finnish Families with Type 1 Diabetes

et al. 2000

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An open problem of some interest in the study of HLA has been the possible existence of transmission distortion in the human HLA complex. In this paper, transmission probabilities are estimated and tested using data on HLA A, B and DR loci genotypes of parents and offspring ascertained from the entire population of Finland (Childhood Diabetes in Finland Study) through one or more offspring diagnosed with insulin-dependent diabetes mellitus (IDDM) during the recruitment period from September 1986 to July 1989. First, we show how to get unbiased estimates of transmission probabilities from the family data collected in the disease registry of incident cases. This is accomplished by assuming that transmission of HLA genes to children in the general population is conditionally independent given the parents’ genotypes, and the birth dates of all offspring. Based on the sampling (ascertainment) process in the study on Childhood Diabetes in Finland, younger siblings of the index child (the oldest proband) are independent of the ascertainment and therefore give rise to unbiased inference regarding allele transmission. The hypothesis of Mendelian transmission of alleles at each locus was tested using the standard χ² test. Goodness-of-fit of the Mendelian inheritance model to the individual locus data is calculated by maximizing the likelihood function over allele transmission intensities at each locus. The existence of a strong transmission distortion is not supported by this study at the loci considered.

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Genetic variability in the major histocompatibility complex: A review of non-pathogen-mediated selective mechanisms

Alberts

Ober

1993

Am. J. Phys. Anthropol.

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The extraordinary genetic polymorphism observed in the major histocompatibility complex (MHC) of the vertebrate genome has attracted the attention of researchers for decades. In almost all taxa that have been investigated, levels of polymorphism are remarkably high. Several mechanisms have been proposed to explain the maintenance of genetic diversity at the MHC, including pathogen-driven natural selection, selection driven by maternal-fetal interactions, and negative assortative mating. In this review we discuss the evidence for the latter two mechanisms in human and animal populations. We begin with a description of the structure and function of the MHC, particularly in humans. Then, evidence for natural selection acting on MHC genes, in the form of homozygote deficiencies observed in human population isolates, is discussed. The two major candidates for mechanisms of non-pathogen-driven selection, maternal-fetal interactions and MHC-based mate choice, are described in detail and their implications are discussed. o 1993 Wiiey-Lisa, IncThe major histocompatibility complex (MHC) encompasses a cluster of genes that have remarkable genetic characteristics. Present in all vertebrates examined to date, the MHC has been a major focus of investigations by geneticists, evolutionary biologists, and anthropologists, who have characterized and tried to elucidate the mechanisms that underlie these extraordinary features. Among its characteristics is the extreme polymorphism of many genes in the complex, which have large numbers of alleles, most of which are present at appreciable frequencies in natural populations. Up to 92 identified alleles per locus are present in mice, and high levels of polymorphism and heterozygosity have been found in almost all other taxa that have been investigated (Klein, 1986). The human MHC, known as the human leukocyte antigen (HLA) region, includes at least 20 HLA-A, 40 HLA-B, 10 HLA-C, 14 HLA-DR, 7 HLA-DQ, and 6 HLA-DP alleles identifiable by serological techniques (Bodmer et al., 1991). Additional alleles can be identified by isoelectric focusing (Yang, 1987) and molecular genetic analysis (Tsuji et al., 1992). Rarely does the frequency of any one allele exceed 30% in any population. As a result, homozygotes for HLA alleles are infrequent in the population and most individuals are heterozygous at each locus.Considerable interest has been generated in possible mechanisms for maintaining the high levels of polymorphism and heterozygosity at MHC loci. Nei (1988,1989) demonstrated that polymorphism in some human MHC regions is 0 1993 Wiley-Liss, Inc.

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A comprehensive search for segregation distortion in HLA

Cited by 30 publications

References 27 publications

Inheritance of MHC class II genes in IDDM studied in population-based affected and control families

Inheritance of MHC class II genes in IDDM studied in population-based affected and control families

Estimation of Transmission Probabilities in Families Ascertained through a Proband with Variable Age-at-Onset Disease: Application to the HLA A, B and DR Loci in Finnish Families with Type 1 Diabetes

Genetic variability in the major histocompatibility complex: A review of non-pathogen-mediated selective mechanisms

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