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Path analysis gives evidence of genetic heritability (.425) for serum IgE levels. Complex segregation analysis indicates, in addition to significant polygenic heritability, a major regulatory locus RE, with homozygotes re/re maintaining persistently high levels of IgE. The gene frequency of re is .489, and the displacement is 1.67 standard deviations.
In families of HLA-B27+ ankylosing spondylitis (AS) patients, the occurrence of secondary cases of sacro-iliitis (SI) among B27+ first degree relatives is more than tenfold higher than expected from the population association of AS with HLA-B27. Secondary cases of SI also occur in relatives of HLA-B27- AS patients. We addressed the question whether other genetic factors than HLA-B27 played a role in the familial occurrence of AS and SI in B27+ and B27- AS cases. To this we tested 24 genetic marker systems including GM and PI in first degree relatives of AS patients: 118 first degree relatives with 16 secondary SI cases in families of 23 B27+ AS probands and 74 relatives with 6 secondary SI cases in families of 14 B27- AS probands. With a LIPED analysis we found no significant evidence for linkage for any of the markers tested, including HLA. In a co-segregation analysis we found a significant deviation from random segregation for HLA-B27 (p = 0.0005) and for HLA haplotypes (p = 0.052) to affected B27+ AS/SI siblings. No such deviation was found to B27- AS/SI cases. For GM and PI we found no significant cosegregation with AS/SI in B27+ and B27- families. In conclusion, apart from HLA-B27, we found no significant effect of any of the genetic marker systems tested in explaining the familial clustering of AS and SI among B27+ and B27- AS patients.
Pea (Pisum sativum L.) is one of the most important edible legumes in China, with both planting area and total yield ranking among the highest in the world. Fusarium wilt, caused by Fusarium oxysporum f. sp. pisi (Fop), is a severe factor limiting pea production. The deployment of resistant pea cultivars is the most effective and sustainable strategy for controlling this disease. In the present study, a novel resistance gene PsFwC9, conferring resistance to Fop race 5, was identified in the resistant pure line Chengwan 9-8 (CW9-8), and its candidate gene Psat4g213640 was characterized and functionally validated to be associated with disease resistance. Genetic analysis of the F₂ population derived from the cross between the resistant parent CW9-8 and the susceptible parent Chengwan 9-1 (CW9-1) revealed that PsFwC9 was controlled by a single dominant gene. Based on whole-genome resequencing, bulked segregant analysis sequencing (BSA-seq) and fine mapping, PsFwC9 was localized to an 817.06-kb region on chromosome 4 (i.e. linkage group IV, chr4LG4), flanked by KASP markers A016508 and A016511, and co-segregated with four markers. Haplotype analysis revealed that only the marker A016615 was significantly associated with Fusarium wilt resistance, and this marker was designated as a diagnostic marker for PsFwC9. Marker A016615 was located at 425 699 725 bp on chr4LG4, corresponding to the 277 bp within Psat4g213640, where a 'A/G' single-nucleotide polymorphism caused an amino acid substitution leading to an alteration in protein structure; therefore, Psat4g213640 was identified as the PsFwC9 candidate gene. Quantitative real-time PCR analysis showed no significant difference in the expression levels of Psat4g213640 between CW9-8 and CW9-1. Overexpression of the candidate gene Psat4g213640CW9-8 in the hairy root system significantly enhanced the resistance of CW9-1 to Fusarium wilt, whereas RNA interference-mediated silencing of Psat4g213640CW9-8 reduced the resistance of CW9-8, indicating that Psat4g213640CW9-8 played a crucial role in pea resistance to Fusarium wilt. In addition, subcellular localization showed that the protein encoded by Psat4g213640 was targeted to the endoplasmic reticulum. Collectively, these findings not only enriched the gene resources for disease resistance in pea and provided an important foundation for elucidating the molecular mechanism of PsFwC9-mediated resistance, but also provided important technical support for the practical application of molecular breeding for disease resistance in pea.
Abdominal fat has been shown to be an important risk factor for many chronic conditions, including diabetes, heart disease, and breast cancer. The objective of this study was to provide evidence for a major gene influence on the ratio of waist to hip circumference (WHR), a measurement commonly used in large scale studies to indicate the presence of abdominal fat. Segregation analysis was conducted on three subsets of families from the Minnesota Breast Cancer Family Study. One analysis was conducted among families with WHR measurements on all women. Two additional analyses were conducted on subsets of women stratified on menopausal status. Multiple regression analysis was used to identify factors associated with WHR expressed as a continuous trait. Complex segregation analyses were performed on the continuous trait of WHR and the covariates identified in the regression analysis. In the analysis of all women, all hypotheses were rejected. Among premenopausal women, the environmental hypothesis with no heterogeneity between generations fit the data best (P = 0.85). However, among postmenopausal women, the requirements for conclusion of the presence of a major gene were met. All non-Mendelian hypotheses were rejected (P < 0.0001), but the additive hypothesis was not rejected (P = 0.19) and provided the best fit to the data. The putative major gene identified by this model accounted for 42% of total phenotypic variance in WHR among these postmenopausal women. The allele for high WHR had a frequency of 27%. These findings support the hypothesis that the distribution of abdominal fat in postmenopausal women is under genetic control.
The joint segregation analysis of a mixed genetic model of major gene plus poly-gene was conducted to study the inheritance of oil content in Brassica napus L.. Five populations, i.e the populations of 2 parents (P1 and P2), F1, F2 and F2:3 (derived from F2) family, from each of the two crosses (1141B x Ken C-1, 32B x Ken C1-2) were investigated.The frequency distributions of oil content in F2 and F2:3 family populations show characteristics of a mixed normal distribution, which indicated that the inheritance of oil content followed a major gene plus poly-gene model. Twenty-one genetic models were established, which could be classified into five types: one and two major genes, polygenes, one and two major genes plus polygenes. The most suitable genetic model could be selected using Akaike's Information Criterion and the fitness of the selected one could be examined by a set of tests. Results show that genetic model D-2 is the most fitting genetic model for the trait. In other words, oil content in oilseed rape is controlled by one additive major gene plus additive and dominance polygenes. For cross 1 (1141B x Ken C1-1) the heritabilities of major gene and poly-genes in F2 are 68.21% and 27.17%, respectively, and in F2:3 are 81.70% and 16.80%, respectively. The additive effect of major gene is -1.74, which indicates that the locus of the allele in parent 1141B may decrease the oil content, but that in parent Ken C1-1 may increase it. The additive and dominance effects of the polygenes are 1.20 and -1.93, respectively. For cross 2 (32B x Ken C1-2) the heritabilities of major gene and polygenes in F2 are 66.20% and 28.10%, respectively, and in F2:3 were 81.00% and 14.90%, respectively. The additive effect of major gene was -3.74, which also indicates that the locus of the allele in parent 32B may decrease the oil content, but that in parent Ken C1-2 may increase it. The additive and dominance effects are -1.99 and 0.93, respectively. The heritability of the major gene in F2:3 is higher than that in F2 in both crosses, so it would be more efficent to conduct selection in F2:3 families for high oil content in breeding.
We performed a genetic analysis of 280 families with congenital indirect inguinal hernia ascertained in Shandong province. The multifactorial threshold model and segregation analysis were applied to these families to investigate the mode of inheritance of congenital indirect inguinal hernia. Our results indicate that congenital indirect inguinal hernia is not compatible with a multifactorial threshold model, and the frequent vertical transmission and high segregation ratio suggest autosomal dominant inheritance with incomplete penetrance and sex influence. Through further pedigree analysis of the multiple case families with at least two closely related affected members, we noted preferential paternal transmission of the disease gene, which might suggest the role of genomic imprinting in the aetiology of this condition.
The polymorphic patterns of human salivary amylase of a large number of individuals of Caucasian origin were determined by using isoelectric focusing and polyacrylamide gel electrophoresis. Nine different salivary amylase protein variants were found; three of them are recorded for the first time and their heredity is shown. Some of the variants are encoded by haplotypes expressing three allozymes. Most variants display low frequencies. Analysis of the relative intensities of variant-specific isozyme bands, combined with segregation analysis, show that extensive quantitative variation is present in the population. The numbers of salivary amylase genes in some families showing quantitative variation at the protein level have been estimated by the polymerase chain reaction. We present evidence that quantitative variations in amylase protein patterns do not always reflect variations in gene copy number but that other mechanisms are also involved.
A new source of greenbug (Schizaphis graminum Rondani) resistance derived from Aegilops tauschii (Coss.) Schmal was identified in W7984, a synthetic hexaploid wheat line and one parent of the International Triticeae Mapping Initiative (ITMI) mapping population. Segregation analysis of responses to greenbug feeding in a set of recombinant inbred lines (RILs) identified a single, dominant gene governing the greenbug resistance in W7984, which was placed in chromosome arm 7DL by linkage analysis with molecular markers in the ITMI population. Allelism tests based on the segregation of responses to greenbug feeding in F2 and testcross plants revealed that the greenbug resistance in W7984 and Largo, another synthetic line carrying the greenbug resistance gene Gb3, was controlled by different but linked loci. Using the ITMI reference map and a target mapping strategy, we have constructed a microsatellite map of Gb3 in a mapping population of 130 F7 RILs from Largo x TAM 107 and identified one marker (Xwmc634) co-segregating with Gb3 and four markers (Xbarc76, Xgwm037, Xgwm428 and Xwmc824) closely linked with Gb3. Deletion mapping of selected microsatellite markers flanking the Gb3 locus placed this resistance gene into the distal 18% region of 7DL. Comparative mapping in the ITMI and Largo x TAM 107 populations using the same set of microsatellite markers provided further evidence that greenbug resistance in W7984 and Largo is conditioned by two different loci. We suggest that the greenbug resistance gene in W7984 be designated Gb7. The microsatellite map of Gb3 constructed from this study should be a valuable tool for marker-assisted selection of Gb3-conferred greenbug resistance in wheat breeding.
We report here the molecular mapping of a fertility restorer gene (named Rf1) for Owen cytoplasmic male sterility in sugar beet. Eight AFLP and two RAPD markers, tightly linked to the Rf1 locus, were identified using bulked segregant analysis. Three AFLP markers, mAFEM972, mAFEM976 and mAFEM985, were found to co-segregate with the Rf1 allele in our mapping populations. With the help of RFLP markers, previously mapped on the sugar beet genome, we showed that Rf1 is positioned in the terminal region of linkage group Kiel III/Koeln IV. This map location agrees well with that found for the restorer gene X, which suggests that the Rf1 locus corresponds to the X locus. The availability of the molecular markers will facilitate the selection of maintainer-pollinator lines in breeding program and provide the foundation for map-based cloning of the Rf1 gene.
Familial combined hyperlipidemia (FCHL) is the most common genetic form of hyperlipidemia in which affected individuals manifest multiple lipoprotein phenotypes. Although the molecular defect is still unknown, several kinetic studies have demonstrated increased turnover rates of apolipoprotein B (apo B) in patients with FCHL, irrespective of their lipoprotein phenotype. Using 3 restriction fragment length polymorphisms (RFLPs) of the apo B gene (XbaI, MspI and EcoRI) we have investigated 33 families which fulfill the diagnostic criteria of FCHL. No significant difference in allele frequency was found between 33 unrelated individuals with FCHL and 107 normolipidemic controls. 3-RFLP haplotypes were constructed in each pedigree. A co-segregation analysis was performed in 7 informative families. In no family was co-segregation observed between the haplotype of the apo B gene and the phenotype of FCHL. These data are not compatible with the hypothesis that FCHL is caused by mutations of the apo B gene acting as a simple mendelian trait.
OBJECTIVES: To confirm, in a study of a large, independent cohort of families with prostate cancer, the findings of three segregation analyses that have suggested the existence of an inherited form of prostate cancer with an autosomal dominant inheritance mode. METHODS: Between January 1991 and December 1993, 1199 pedigrees were ascertained through single, unrelated, prostate cancer probands who presented for radical prostatectomy at the Division of Urologic Surgery, Washington University Medical Center in St. Louis, Missouri. Maximum likelihood segregation analysis was used to test specifically for mendelian inheritance of prostate cancer. RESULTS: Segregation analyses revealed that the familial aggregation of prostate cancer can be best explained by the autosomal dominant inheritance of a rare (q = 0.0037) high-risk allele. According to the best-fitting autosomal dominant model, 97% of all carriers will be affected by 85 years of age compared with 10% of noncarriers. Furthermore, the autosomal dominant model predicts that the high-risk allele accounts for a large proportion (65%) of all patients diagnosed with prostate cancer before 56 years of age. However, of all prostate cancer cases, a relatively small proportion is inherited (8% by 85 years old). CONCLUSIONS: These results are in agreement with earlier reports of segregation analyses of prostate cancer and strengthen the evidence that prostate cancer is inherited in a mendelian fashion within a subset of families.
BACKGROUND: Alport syndrome (AS) is a clinically and genetically heterogeneous renal disorder, predominantly affecting the type IV collagen alpha 3/alpha 4/alpha 5 network of the glomerular basement membrane (GBM). AS can be caused by mutations in any of the three genes encoding these type IV collagen chains. The majority of AS families (85%) are X-linked (XL-AS) involving mutations in the COL4A5 gene. Mutations in the COL4A3 and COL4A4 genes cause autosomal recessive AS (AR-AS), accounting for approximately 14% of the cases. Recently, autosomal dominant AS (AD-AS) was linked to the COL4A3/COL4A4 locus in a large family. METHODS: COL4A3 and COL4A4 cDNAs were generated by nested reverse transcription-polymerase chain reaction and were analyzed by DNA sequence analysis. Denaturating high-performance liquid chromatography (DHPLC) was used for mutation and segregation analysis at the genomic DNA level. RESULTS: In the AD-AS family, a splice site mutation resulting in skipping of exon 21 of the COL4A3 gene was detected. The mutation does not alter the reading frame and is predicted to result in a COL4A3 chain with an internal deletion. CONCLUSION: As the NC domain is intact, this chain may be incorporated and distort the collagen triple helix, thereby causing the dominant effect of the mutation. The finding of a specific COL4A3 mutation in AD-AS completes the spectrum of type IV collagen mutations in all genetic forms of AS.
In many strain combinations among inbred rats, intravenously injected 51Cr-labelled lymphocytes are destroyed in substantial numbers by unsensitized allogeneic hosts. Destruction of cells (referred to as natural cytotoxicity (NC)) occurs within a few hours of injection, and is characterised by a decreased accumulation of radioactivity in the lymph nodes and increased renal excretion of label by allogeneic hosts, as compared with the distribution of label in syngeneic recipients of the same cell suspension. An intact spleen is necessary for killing. The level of NC expressed is consistent for a given donor-host combination. Using arbitrary criteria to compare the levels of NC expressed by different donor-host combinations among inbred rats, 13 of 95 strain combinations have been shown to express high NC, 63 intermediate NC and 19 low NC. The level of NC expressed cannot be correlated with the extent to which donor and host differ in respect of known MHC genes. Segregation analysis has shown high NC to be controlled by at least 2 independently segregating genes, one of which is MHC-linked. It is possible to weaken or abrogate NC by the neonatal injection of bone-marrow cells from the donor strain, and to reverse this reduced reactivity by the injection of host strain lymphocytes. The substitution of either the donor (P1) or the host (P2) by the P1 X P2)F1 hybrid reduces or eliminates NC in strain combinations normally expressing high NC. It is currently uncertain whether NC can be augmented. In the single strain combination in which maturation has been studied, NC becomes evident during the 4th week of life and attains adult levels during the 6th-7th weeks. NC is at least partially radio-sensitive. Two groups of reactivities appear to be related to NC: (i) those which have been identified in the context of aberrant lymphocyte homing, and for which allogeneic lymphocytes are the targets; (ii) the group of natural resistance systems which includes NK cells, and whose reactivity is directed against a variety of other target cells.
To test the hypothesis that genetic factors are operative in the predisposition to leprosy (Hansen's disease) in humans, a genetic epidemiologic investigation was performed on 269 leprosy kindreds containing 552 affected individuals from an isolated population in Papua New Guinea. The community, and not the family, was the basic social unit. Leprosy, an infectious disease, was not communal but strongly familial within the Karimui. Segregation analysis, to determine whether a major gene for the susceptibility to leprosy was segregating within a single multi-generational kindred, could not differentiate between a Mendelian genetic and a purely environmental hypothesis. The composite kindred data, however, suggest a genetic hypothesis for the non-immunologically induced susceptibility to leprosy per se. Within familial kindreds leprosy invariably emanated from a common ancestral sibship, and risk was associated with the closeness of kin but not with infectivity or severity.
Six pedigrees including 107 animals of the breed German Brown Swiss were available to test for a single gene conditioning for convergent strabismus with exophthalmus. The regressive logit models of the segregation analysis showed that a major gene model with additively acting genes explained the segregation of affected animals in the pedigrees in the best way. Additionally, polygenic and environmental effects might be of importance in the occurrence of convergent strabismus with exophthalmus.
The L1210 murine lymphoblast cell line possessed a B lymphocyte-specific alloantigen which was detected with C57BL/Ks anti-L1210 serum. The antigen was found on splenic B lymphocytes but not on thymocytes, T lymphocytes, or erythrocytes. It was present on only 7% of bone marrow cells. The reactivity of C57BL/Ks anti-DBA/2-spleen serum was indistinguishable from that of the anti L1210 serum, confirming that the antigen was a normal component of B lymphocytes of the CBA/2 mouse. The strain distribution pattern of the antigen detected by the C57BL/Ks anti-L1210 serum indicated that this alloantigen was not an allele of the H-2K, H-2D, Mls, or Ig loci. Genetic analysis indicated that the antigen was inherited as a single, Mendelian dominant trait. Segregation analysis of (B10.BR X DBA/2)F1 X AKR/J offspring indicated that this B cell marker was not linked to geneslambdacoding for H-2.31 or Ly 4.2. The C57BL/Ks anti-L1210 serum identified a new polymorphic genetic locus, the product of which was B lymphocyte specific.
We have investigated 31 families segregation for Hunter Syndrome in order to advance our understanding of the genetics of this disease. The hair root test for the diagnosis of carriers of Hunter Syndrome was improved by the adoption of a new diagnostic index that distinguishes between carrier and normal females better than previous methods of analysis. One hundred and eleven female relatives of the affected children were tested by such procedures. This showed that seven out of 31 mothers were not carriers (22.6%), thus suggesting a small deficit of new mutation relative to the expectation that 33% of lethal, recessive alleles arise anew in a population at equilibrium at a sex-linked locus with equal mutation rates in male and female gametogenesis. The difference, however, is not statistically significant. The age of the parents of new mutants was slightly but significantly raised. Nevertheless, the independent increase in the age of the fathers of new female mutants was not statistically significant. Finally, a deficit of affected males was observed. This was significant and suggests the possibility of intrauterine loss of some affected males. Linkage analysis between the Hunter Syndrome locus, three polymorphisms in the Factor IX gene and the anonymous polymorphic probes 52A and DX13 showed that the Hunter locus is fairly closely linked to DX13, and hence distal to the Factor IX gene, while no linkage was observed with the 52A polymorphic site. The maximum lod score for the linkage between factor IX and the Hunter Syndrome locus was 0.424 at theta = 0.25; and that for the linkage between the Hunter Syndrome locus and DX13 was 3.01 at theta = 0.1.
A questionnaire survey characterized a sample of 670 probands with retinitis pigmentosa (RP) and allied disorders. Segregation analysis provided some evidence for a small proportion of sporadic cases and for decreased segregation ratios of the dominant and recessive genotypes, which could be attributed to delayed age of onset in some cases. The overall incidence of RP was indirectly calculated to be approximately 1 in 3,700, while the incidence of autosomal recessive RP, including at least two genocopies, was estimated to be about 1 in 4,450. Family data analysis included the calculation of the likelihood that each family represented autosomal recessive, autosomal dominant, and X-linked inheritance patterns. These likelihoods were then converted to relative probabilities and summed over the sample population to yield estimates of the proportions of the three Mendelian types. This large, heterogeneous sample indicated that approximately 84% of the cases in the United States may be autosomal recessive, while about 10% are dominant and 6% X-linked recessive.