HLA sharing in multiplex sibships

Suarez, Brian K.; Crouse, Jill D.; Eerdewegh, Paul Van

doi:10.1111/j.1469-1809.1983.tb00982.x

Cited by 9 publications

(3 citation statements)

References 8 publications

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“…The concordance between the sib genotypes could be total (ibs = 1), partial (ibs = 1/2), or absent (ibs = 0). Under the null hypothesis of no linkage, the mean number of identical marker alleles shared by a set of sib pairs (and its variance) is not affected by whether or not some of the sib pairs belong to the same sibship (Suarez et al 1983;Blackwelder 1985). Thus, the renin genotypes were compared for each sib pair and all the information contained in each sibship was taken into account by adding the concordances between all different sib pairs (see Appendix).…”

Section: Comparison Of Sib Genotypesmentioning

confidence: 99%

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Sib pair linkage analysis of renin gene haplotypes in human essential hypertension

et al. 1992

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Although essential arterial hypertension is believed to have a strong genetic predisposition, the gene(s) responsible are unknown. The mechanisms underlying the regulation of blood pressure and experimental studies place the renin gene among the main candidate genes that need to be tested in humans. We tested the hypothesis of a linkage between the renin gene and essential hypertension using the affected sib pair method. Siblings (133 subjects, 52.1 +/- 10.9 years) from 57 families were selected for sustained hypertension (160.7 +/- 22.9/99.5 +/- 12.8 mmHg with 80% of patients under antihypertensive treatment), of early onset (40.7 +/- 12.0 years), in the absence of obesity, diabetes mellitus, and secondary hypertension. Eight renin haplotypes were generated from three diallelic renin restriction fragment length polymorphisms (RFLPs) (TaqI, HinfI, HindIII) located throughout the renin gene. The allelic concordance between the sib pairs was analyzed by identity by state relationships for 98 sib pairs (41 for 41 couples, 39 for 13 trios, 18 for 3 quartets). Allelic frequencies in the 57 hypertensive probands were similar to those observed among 102 hypertensive subjects studied previously. Six of eight possible haplotypes were observed, the informativity of the marker corresponded to 70% of heterozygosity. Allelic concordance for all sib pairs according to sibship size was not significantly different from that expected under the hypothesis of no linkage (t = 0.52, P = 0.15) reflecting only a small excess of renin alleles shared by the hypertensive sibs (1.44 +/- 0.6 vs 1.36 +/- 0.6). Likewise the linkage hypothesis was unsupported by weighted estimates to correct for possible bias due to large sibship size. Thus, the sib pair analysis suggests that the renin gene does not have a frequent role in the pathogenesis of essential hypertension; further more powerful linkage studies or other approaches will be needed to detect contributions at the renin locus to the heritability of essential hypertension.

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Section: Comparison Of Sib Genotypesmentioning

confidence: 99%

“…In addition to wl = 1, we tested w2 = 1/Var(Z~) 1/2 (Suarez et al 1983;Motro and Thompson 1985) and w3 = (s -1)l/2/Var(Zs) 1/2 (Hodge 1984), where s represents the size of the affected sibship and Z, the statistic reflecting the allelic concordance for each sibship size (Lange 1986). …”

Section: Computation Of the Expected Concordance Valuesmentioning

confidence: 99%

Sib pair linkage analysis of renin gene haplotypes in human essential hypertension

et al. 1992

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“…Sibships in which there are three or more affected do not have the same distribution of parental genotypes at the 'disease' locus as those with only two affected (Weitkamp, 1981 ;Rubinstein et al 1981;Suarez et al 1983; Motro & Thomson, 1985;Ewens & Clark, 1984). The analysis of only families with three or more affected sibs can therefore be used to give us additional information regarding the mode of inheritance of the HLA associated diseases.…”

Section: Introductionmentioning

confidence: 99%

The affected sib method. IV. Sib trios

Payami

Thomson

Motro

et al. 1985

Annals of Human Genetics

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The classical sib pair method uses the expected and observed HLA (human leukocyte antigen) haplotype sharing distribution in sib pairs, who are affected with an HLA associated disease, to make inferences about the inheritance of the disease. In this paper we present the expected HLA haplotype sharing distributions in affected sib trios, and sib pairs, from families with three or more affected sibs. The underlying model for both distributions, as for the classical sib pair method, is that disease predisposition is determined by a single allele at an HLA-linked locus. The sib trio tests of hypotheses (additive and recessive), and disease parameter estimates (additive, recessive and intermediate), can be compared with those obtained from the classical sib pair analysis. In addition, the sib trio data allow parameter estimation for a general disease model to be made, if the data fall within the bounds of the expectation. This study forms the basis of later investigations which show that haplotype sharing of affected sib trios for two susceptibility alleles (negative complementation) model, which appears appropriate for insulin dependent diabetes mellitus (IDDM), moves outside the bound of the single susceptibility expectations outlined here, whereas haplotype sharing values for sib pairs are bound by the single susceptibility allele expectations. Available Caucasian IDDM data have been analysed. The results support genetic heterogeneity of IDDM.

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HLA and Major Affective Disorder

Suarez¹

1984

Arch Gen Psychiatry

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HLA sharing in multiplex sibships

Cited by 9 publications

References 8 publications

Sib pair linkage analysis of renin gene haplotypes in human essential hypertension

Sib pair linkage analysis of renin gene haplotypes in human essential hypertension

The affected sib method. IV. Sib trios

HLA and Major Affective Disorder

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