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PubMed1981

Frequency analysis of cytotoxic T lymphocyte precursors in chimeric mice. Evidence for intrathymic maturation of clonally distinct self-major histocompatibility complex- and allo-major histocompatiblilty complex-restricted virus-specific T cells.

To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self-MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL-P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo-MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self-MHC or of allogeneic MHC products.

Animals↗
PubMed1990

Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460.

We recently developed an enzyme-linked immunosorbent assay (ELISA) for total protein S (PS) antigen using the monoclonal antibody S-12. During the screening of thrombophilic patients we identified a patient, who was using marcoumar, with 0% PS by monoclonal ELISA and 23% PS by polyclonal ELISA. Further analysis of this patient and his family showed that the patient was a compound heterozygote for type 1 PS deficiency and for an abnormal PS molecule (PS-Heerlen) that was not recognized by the S-12 antibody. Similar observations were made in two sisters from an unrelated Dutch family. Subsequent studies showed that PS Heerlen has a slightly lower molecular weight (71,000) than normal PS (73,000), binds normally to C4b-binding protein, and retains full activated protein C cofactor activity. The alteration in the PS Heerlen molecule was identified as a substitution of Ser460 by Pro, which is due to a unique T---C transition in exon 13 of the active PS-alpha gene. The substitution occurs in the consensus sequence for the potential N-linked glycosylation of Asn458. Digestion with N-glycanase showed that normal PS probably contains three N-linked oligosaccharide side chains, while PS Heerlen contains only two (Asn458 not glycosylated?). Segregation analysis in the two original families showed that the presence of the genetic abnormality was always associated with the PS-Heerlen phenotype. The frequency of the PS-Heerlen allele was found to be 0.52% in the general population and 0.67% in a population of patients with unexplained thrombophilia. There is no evidence that the PS Heerlen allele is associated with an increased risk for thrombosis.

Adult↗
PubMed1987

Clonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd.

Only two sets of antigenic determinants are recognized by T lymphocytes at uniquely high precursor frequencies: those encoded by the MHC and those encoded by Mls. The structural as well as functional characteristics of MHC products have been extensively analyzed. In contrast, little information concerning the nature of Mls genes or their products is available. Although it was originally described (5, 6) that the Mls locus on chromosome 1 is composed of four alleles that encode polymorphic cell surface structures, the issues of polymorphism and allelism in the Mls system have been controversial for some time. In the present study, T cell clones were generated by continuous stimulation of B10.BR (H-2k, Mlsb) T cells by CBA/J (H-2k, Mlsd) stimulators and they were used to analyze the relationship of putative Mlsa, Mlsc, and Mlsd determinants. All clones proliferated in response to determinants expressed by CBA/J stimulators. In addition, each of these clones exhibited a second reactivity to either AKR/J (H-2k, Mlsa) or C3H/HeJ (H-2k, Mlsc) stimulators. No clone responded to both AKR/J and C3H/HeJ. These second specificities were defined to be for Mlsa or Mlsc determinants, respectively, by the response patterns of clones and unprimed T cells to stimulators derived from congenic strains, recombinant inbred (RI) strains, and backcross mice. Moreover, a segregation analysis of the (CBA/J X B10.BR)F1 X B10.BR backcross indicated that the Mlsa-like and Mlsc-like determinants expressed on CBA/J (Mlsd) cells are in fact encoded by nonallelic, unlinked genes. These findings suggest a new concept of the polymorphism and genetics of the Mls system. It is proposed that two distinct and nonallelic gene products express, respectively, the noncrossreacting Mlsa and Mlsc determinants, and that the Mlsd phenotype does not represent an independent genotype but rather reflects the concurrent expression of Mlsa and Mlsc. The Mls system, therefore, consists of at least two systems that are distinct both genetically and antigenically, and that may be of different biologic or physiologic significance as well.

Alleles↗
PubMed2001

Early and multiple Ac transpositions in rice suitable for efficient insertional mutagenesis.

A GFP excision assay was developed to monitor the excision of Ac introduced into rice by Agrobacterium-mediated transformation. The presence of a strong double enhancer element of the CaMV 35S promoter adjacent to the Ac promoter induced very early excision, directly after transformation into the plant cell, exemplified by the absence of Ac in the T-DNA loci. Excision fingerprint analysis and characterization of transposition events from related regenerants revealed an inverse correlation between the number of excision events and transposed Ac copies, with single early excisions after transformation generating Ac amplification. New transpositions were generated at a frequency of 15-50% in different lines, yielding genotypes bearing multiple insertions, many of which were inherited in the progeny. The sequence of DNA flanking Ac in three representative lines provided a database of insertion tagged sites suitable for the identification of mutants of sequenced genes that can be examined for phenotypes in a reverse genetics strategy to elucidate gene function. Remarkably, two-thirds of Ac tagged sites showing homology to sequences in public databases were in predicted genes. A clear preference of transposon insertions in genes that are either predicted by protein coding capacity or by similarity to ESTs suggests that the efficiency of recovering knockout mutants of genes could be about three times higher than random. Linked Ac transposition, suitable for targeted tagging, was documented by segregation analysis of a crippled Ac element and by recovery of a set of six insertions in a contiguous sequence of 70 kb from chromosome 6 of rice.

Base Sequence↗
PubMed2005

Molecular analysis of the high stearic acid content in sunflower mutant CAS-14.

Increasing the stearic acid content to improve sunflower (Helianthus annuus L.) oil quality is a desirable breeding objective for food-processing applications. CAS-14 is a sunflower mutant line with a high stearic acid content in its seed oil (>35% vs. <6% in currently grown sunflower hybrids), which is controlled by the Es3 gene. However, the expression of the high stearic acid character in CAS-14 is strongly influenced by temperature during seed maturation and it is not uniform along the seed. The objectives of this study were (1) to identify PCR-based molecular markers linked to the Es3 gene from CAS-14, (2) to map this gene on the sunflower genetic map, and (3) to characterize the interaction between CAS-14 and CAS-3, a sunflower high stearic acid (about 26%) mutant line with the Es1 and Es2 genes determining this trait. Two F2 mapping populations were developed from crosses between CAS-14 and P21, a nuclear male sterile line with the Ms11 gene controlling this character, and between CAS-14 and CAS-3. One hundred and thirty-three individuals from P21xCAS-14, and 164 individuals from CAS-3xCAS-14 were phenotyped in F2 and F3 seed generations for fatty acid composition using gas-liquid chromatography, and they were then genotyped with microsatellite [simple sequence repeat (SSR)] and insertion-deletion (INDEL) markers. Bulk segregant analysis in the P21xCAS-14 population identified two markers on LG 8 putatively linked to Es3. A large linkage group was identified using additional markers mapping to LG 8. Es3 mapped to the distal half of LG 8 and was flanked by the SSR markers ORS243 and ORS1161 at genetic distances of 0.5, and 3.9 cM, respectively. The Ms11 gene was also mapped to LG 8 and genetic distance between this gene and Es3 was found to be 7.4 cM. In the CAS-3xCAS-14 population, two QTLs were identified on LG 1 and LG 8, which underlie the Es1 gene from CAS-3 and the Es3 gene from CAS-14, respectively. A significant epistatic interaction between these two QTLs was found. Results from this study provided a basis for determining CAS-14 efficient breeding strategies.

Breeding↗
PubMed2000

A homokaryotic derivative of a Phanerochaete chrysosporium strain and its use in genomic analysis of repetitive elements.

Analysis of complex gene families in the lignin-degrading basidiomycete Phanerochaete chrysosporium has been hampered by the dikaryotic nuclear condition. To facilitate genetic investigations in P. chrysosporium strain BKM-F-1767, we isolated a homokaryon from regenerated protoplasts. The nuclear condition was established by PCR amplification of five unlinked genes followed by probing with allele-specific oligonucleotides. Under standard nitrogen-limited culture conditions, lignin peroxidase, manganese peroxidase, and glyoxal oxidase activities of the homokaryon were equivalent to those of the parental dikaryon. We used the homokaryon to determine the genomic organization and to assess transcriptional effects of a family of repetitive elements. Previous studies had identified an insertional mutation, Pce1, within lignin peroxidase allele lipI2. The element resembled nonautonomous class II transposons and was present in multiple copies in strain BKM-F-1767. In the present study, three additional copies of the Pce1-like element were cloned and sequenced. The distribution of elements was nonrandom; all localized to the same 3.7-Mb chromosome, as assessed by segregation analysis and Southern blot analysis of the homokaryon. Reverse transcription-PCR (RT-PCR) showed that Pce1 was not spliced from the lipI2 transcript in either the homokaryon or the parental dikaryon. However, both strains had equivalent lignin peroxidase activity, suggesting that some lip genes may be redundant.

Chromosome Mapping↗
PubMed2002

High throughput mutation screening of the factor VIII gene (F8C) in hemophilia A: 37 novel mutations and genotype-phenotype correlation.

Hemophilia A (HEMA) is an X-linked bleeding disorder caused by mutations in the factor VIII gene (F8C). Molecular genetic testing for the factor VIII gene is challenging due to its large size. Here we present results of high throughput mutation scanning based on Southern blot analysis and direct sequencing of all PCR amplified coding exons and the exon-intron boundaries of the factor VIII gene. The results of mutation analysis on 89 hemophiliac males showed presence of a disease-causing mutation in 80 individuals (90%, 95% CI of 82%-95%). Seven out of nine mutation-negative individuals were severe cases of hemophilia A with < 1% factor VIII protein in the blood. The correlation of phenotype with genotype as observed in this study was not absolute. This finding is supported by similar observations in the international database for hemophilia A mutations (HAMSTeRS). This issue raises the importance of genotypes at other loci that can act as modifiers for the phenotype. Thirty-four novel mutations and three novel substitutions for previously reported amino acid residues were identified in this series of 80 mutations. The mutations cover the full spectrum including rearrangements, deletions, frameshift, and point mutations. The novel missense mutations require careful evaluation. Prediction of a mutation as the disease-causing allele was made from the nature of the substitution and the degree of conservation of the mutated amino acid among species that have diverged in evolution. In some cases segregation analysis of the mutation with disease condition was performed when other family members were available.

Child↗
PubMed2002

A complete mutation screen of the ADPKD genes by DHPLC.

BACKGROUND: Genetic analysis is a useful diagnostic tool in autosomal dominant polycystic kidney disease (ADPKD), especially when imaging results are equivocal. However, molecular diagnostics by direct mutation screening has proved difficult in this disorder due to genetic and allelic heterogeneity and complexity of the major locus, PKD1. METHODS: A protocol was developed to specifically amplify the exons of PKD1 and PKD2 from genomic DNA as 150 to 450 bp amplicons. These fragments were analyzed by the technique of denaturing high-performance liquid chromatography (DHPLC) using a Wave Fragment Analysis System (Transgenomics) to detect base-pair changes throughout both genes. DHPLC-detected changes were characterized by sequencing. RESULTS: Cost effective and sensitive mutation screening of the entire coding regions of PKD1 and PKD2 by DHPLC was optimized. All base-pair mutations to these genes that we previously characterized were detected as an altered DHPLC profile. To assess this method for routine diagnostic use, samples from a cohort of 45 genetically uncharacterized ADPKD patients were analyzed. Twenty-nine definite mutations were detected, 26 PKD1, 3 PKD2 and a further five possible missense mutations were characterized leading to a maximal detection rate of 76%. A high level of polymorphism of PKD1 also was detected, with 71 different changes defined. The reproducibility of the DHPLC profile enabled the recognition of many common polymorphisms without the necessity for re-sequencing. CONCLUSIONS: DHPLC has been demonstrated to be an efficient and effective means for gene-based molecular diagnosis of ADPKD. Differentiating missense mutations and polymorphisms remains a challenge, but family-based segregation analysis is helpful.

Chromatography, High Pressure Liquid↗
PubMed2006

18q deletions: clinical, molecular, and brain MRI findings of 14 individuals.

We studied 14 individuals with partial deletions of the long arm of chromosome 18, including terminal and interstitial de novo and inherited deletions. Study participants were examined clinically and by brain MRI. The size of the deletion was determined by segregation analysis using microsatellite markers. We observed that the phenotype was highly variable, even in two families with three 1st degree relatives. Among the 14 individuals, general intelligence varied from normal to severe mental retardation. The more common features of 18q-deletions (e.g., foot deformities, aural atresia, palatal abnormalities, dysmyelination, and nystagmus) were present in individuals lacking only the distal portion 18q22.3-qtel. Interstitial deletions exerted very heterogeneous effects on phenotype. In individuals with distal 18q22.3-q23 deletions, brain MRI was very distinctive with poor differentiation of gray and white matter on T2-weighted images.

Abnormalities, Multiple↗
PubMed1983

Admixture analysis of high density lipoprotein cholesterol distribution in a Jerusalem population sample.

The distribution of high density lipoprotein cholesterol values (HDL-C) in 2003 nuclear families (including both parents and one child aged 17) participating in the Jerusalem Lipid Research Clinic survey, were analyzed by a maximum-likelihood procedure for evidence of bimodality. HDL-C was age-sex adjusted by the mean-variance method to 17 year old male levels. After covariance adjustment for Quetelet's index, season, education and social class, when using untransformed data a mixture of two distributions fitted the data significantly better than one distribution in both sexes. The results indicated that 4.7% of males and 14.1% of females came from an upper distribution with mean values of 2.15-3.15 standard deviations above the major mode. We next applied the MacLean et al. (1976) method of transformation and used a maximum-likelihood method in which the skewness parameter was estimated jointly with the other parameters of the model. When the data were transformed the mixture of two distributions fitted the data significantly better than one for males only. We tested a mixture of three normal distributions and estimated that 6% of both males and females belonged to a higher distribution, while 1% came from a lower distribution. This model did not provide a significantly better fit to the data than a mixture of two distributions. Our findings imply that in the Israeli population there is evidence for an admixture in the distribution of HDL-cholesterol. Segregation analysis is necessary in order to determine whether a major gene or some environmental factors are responsible for the commingling detected.

Adolescent↗
PubMed1994

A study of hereditary essential tremor.

Twenty index patients with hereditary essential tremor and their kindreds were studied to define the phenotype of this condition. Ninety-three first degree and 38 more distant relatives were examined; 53 definite and 18 possible secondary cases were identified. The age of tremor onset was bimodally distributed with a median at approximately 15 years. Segregation analysis indicated autosomal dominant inheritance and penetrance was virtually complete by the age of 65 years. There were no examples of the disease skipping a generation. Men and women were affected in equal proportions. About 50% of cases were alcohol responsive. In the majority of families alcohol responsiveness was either consistently present or did not occur, but in 20% of kindreds definite heterogeneity of responsiveness was encountered within each family. The typical phenotype was a mild symmetrical postural tremor of the upper limbs. Tremor of the legs, head, facial muscles, voice, jaw and tongue occurred but never in isolation and rest, task specific (e.g. primary writing tremor) and primary orthostatic tremors were not found. Head tremor was invariably mild and 75% was of a 'no-no' type. Dystonia (e.g. torticollis and writer's cramp) were not encountered, a finding which strongly suggests that many previous studies of 'essential tremor' were contaminated by cases of idiopathic or hereditary torsion dystonia. No association with Parkinson's disease was found but classical migraine occurred in approximately 26% of cases and co-segregated with tremor. The severity of arm tremor (assessed using a clinical rating scale and by scoring tremor in Archimedes spirals) and disability increased with advancing age and increasing tremor duration, but there was no correlation between age at tremor onset and either tremor severity or disability. Men and women were affected with equal severity. The sex of the affected parent had no influence on the severity of tremor or the degree of disability experienced by an affected child. Disability commenced in the second decade and progressively increased. All the index patients and 59% of the definite secondary cases had tremor induced disabilities. Eighty-five percent of index patients and 38% of secondary cases also reported some degree of social handicap. Twenty-five percent of index patients and 12% of secondary cases had been compelled to change jobs or retire. Biological fitness was normal.

Adolescent↗
PubMedDate not supplied

Lung injury leading to respiratory distress syndrome in young Dalmatian dogs.

A progressive pulmonary disease resulting in severe respiratory failure and death in an average of 3 weeks was diagnosed in 11 young Dalmatian dogs. The dogs were from 4 litters, all genetically related by a common ancestor. The initial clinical signs were tachypnea and noisy respiration. Respiratory distress developed shortly before death and was characterized by strenuous and rapid respirations, along with cyanosis and vomiting. On blood gas analysis, there were severe arterial hypoxemia, hypercapnia, and marked alveolar-arterial oxygen difference. Radiographically, a diffuse pattern of alveolar, interstitial, and peribronchial densities was observed in the lungs. Most dogs developed pneumomediastinum and gastroesophageal intussusception in the terminal phase of the disease. There was no response to treatment with antibiotics, corticosteroids, diuretics, or oxygen. At necropsy, the lungs were wet, heavy, and relatively airless. Absence of 1 kidney in 2 dogs and severe internal hydrocephalus in 2 dogs were additional necropsy findings. Pulmonary histopathology included metaplasia and atypia of the alveolar and bronchiolar epithelium, a nonpurulent inflammatory reaction characterized mainly by mononuclear cells and macrophages, eosinophilic hyaline membrane formation, and focal pulmonary fibrosis. The histological manifestations were typical of acute lung injury. Clinically, the findings were consistent with adult respiratory distress syndrome (ARDS), except for the relatively long course. No known risk factors for ARDS, such as trauma, toxin exposure, infection, or endotoxemia could be identified. The relationship of the other abnormalities (ie, renal aplasia, hydrocephalus) to the pulmonary disease also remains obscure. An inherited defect is suspected, because segregation analysis of the 4 litters suggests autosomal recessive inheritance.

Age Factors↗
PubMed1996

Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures.

Insulin resistance is part of a metabolic syndrome that also includes non-insulin-dependent diabetes mellitus, dyslipidemia, obesity, and hypertension. It has been hypothesized that insulin resistance represents the primary physiological defect underlying this syndrome. Since insulin resistance is at least partially genetically determined, we hypothesized that genes influencing insulin resistance would have pleiotropic effects on a number of other traits, including triglyceride (TG) and HDL cholesterol levels, body mass index (BMI) and body fat distribution, and blood pressure levels. To investigate this hypothesis, we analyzed data obtained from individuals in 41 families enrolled in the San Antonio Family Heart Study. Statistical methods that take advantage of the relatedness among individuals were used to differentiate between genetic and nongenetic (ie, environmental) contributions to phenotypic variation between traits. Serum levels of fasting and 2-hour insulin (measured in 767 and 743 nondiabetic family members, respectively) were used as a measure of insulin resistance. The genetic correlations were high between insulin levels (both fasting and 2-hour) and each of the following: BMI, HDL level, waist-to-hip ratio, and subscapular-to-triceps ratio, indicating that the same gene, or set of genes, influences each pair of traits. In contrast, the genetic correlations of insulin levels with systolic and diastolic blood pressures were low. We have previously shown that a single diallelic locus accounts for 31% of the phenotypic variation in 2-hour insulin levels in this population. We conducted a bivariate segregation analysis to see if the common genetic effects on insulin and these other traits could be attributable to this single locus. These results indicated a significant effect of the 2-hour insulin locus on fasting insulin levels (P = .02) and BMI (P = .05), with the "high" insulin allele associated with higher levels of fasting insulin but lower levels of BMI. There was no detectable effect of this locus on HDL level, TG level, subscapular-to-triceps ratio, or blood pressure. Overall, these results suggest that a common set of genes influencing insulin levels also influences other insulin resistance syndrome-related traits, although for the most part this pleiotropy is not attributable to the 2-hour insulin level major locus.

Adult↗
PubMed1993

Segregation of delta F508 and normal CFTR alleles in human sperm.

Single sperm typing provides an accurate method to order tightly linked loci by single cell DNA high resolution segregation analysis. We have used similar methods to type individual sperm from a known delta F508 cystic fibrosis heterozygote to determine the frequency of the mutation within his germ cell population, and to test possible explanations for the reported sex ratio distortion of the cystic fibrosis (CF) mutation to male offspring. Using a nested polymerase chain reaction we have been able to amplify a single locus sequence, cystic fibrosis transmembrane conductance regulator (CFTR), from a single target sperm haploid genome to detectable amounts without the use of radioactivity. The same sperm from a single male delta F508 carrier were simultaneously typed for the presence of the sex chromosomes to verify the ratio of X- to Y-bearing sperm and to determine the association, if any, between sex and delta F508 in male gametes. We have demonstrated that there is a significant difference in the proportions of 'normal' and 'delta F508' sperm (X2 = 7.36, p < 0.01), although when the same sperm are sexed the difference between delta F508/X and delta F508/Y sperm is not significant (X2 = 1.71, p = 0.192). Single sperm typing can address questions about segregation distortion in man, and it is unlikely that sex ratio distortion for CF carriers is due to events which occur pre-fertilisation. As these data are from one individual only, they should be confirmed for other male carriers, including those with different CF mutations.

Alleles↗
PubMedDate not supplied

Genetics of nonsyndromic cleft lip with or without cleft palate: is there a Mendelian sub-entity?

The mode of inheritance of nonsyndromic cleft lip with or without cleft palate (NSCLP) is still a matter of dispute. We performed segregation analysis on three data sets of families ascertained through an affected child with NSCLP. The first two data sets were selected in France and were pooled for a global analysis. No major gene effect could be evidenced in spite of a very large number of families (666 pedigrees including 719 nuclear families). The third data set was British and consisted of three-generation families including the offspring of probands. A major gene effect, as well as a strong residual multifactorial component, were highly significant and we could show that this evidence almost entirely came from the information on probands' offspring. We conclude that a mixture of monogenic and of multifactorial cases is probably the best explanation for the observations made in this study. Analyses performed in pedigrees with multiple cases closely related might allow reducing heterogeneity and help identifying those Mendelian sub-entities.

Child↗
PubMed2004

Evaluating the genetic basis of multiple-locule fruit in a broad cross section of tomato cultivars.

Lycopersicon esculentum accessions bearing fasciated (multiloculed) fruit were characterized based on their flower organ and locule number phenotypes. Greenhouse and field evaluations indicate that increases in locule number are associated with increases in the number of other floral organs (e.g., sepals, petals, stamens) in all stocks. F1 complementation, F2 segregation analysis, and genetic mapping indicate that at least four loci account for increases in the number of carpels/locules in these stocks. The most significant of these map to the bottoms of chromosomes 2 and 11 and correspond to the locule number and fasciated loci. All stocks tested were fixed for mutations at the fasciated locus, which maps to the 0.5-cM interval between the markers T302 and cLET24J2A and occurs in at least three allelic forms (wild type and two mutants). One of the fasciated mutant alleles is associated with nonfused carpels and repressed recombination and may be due to a small inversion or deletion. The other two loci controlling locule number correspond to the lcn1.1 and lcn2.2 loci located on chromosomes 1 and 2, respectively.

Chromosome Mapping↗
PubMed1984

Platelet monoamine oxidase (MAO) activity: evidence for a single major locus.

Monoamine oxidase (MAO), a mitochondrial enzyme involved in the degradation of biogenic amines, has been associated with psychiatric morbidity. Although twin and family studies have indicated that MAO activity is familial, the exact mode of transmission is unclear. We performed segregation analysis on 154 nuclear families containing 419 individuals using the mixed model, which allows for a single major locus with a polygenic background. We were able to reject a dominant and additive locus with or without a heritable background and a recessive locus without background. The acceptable models were: (1) a codominant model without background where the mean of the heterozygote distribution was 30% of the distance from the low to the high homozygote distributions, and (2) a recessive locus with heritable background. In both cases, the gene frequency for the high-MAO allele is approximately .25--at odds with suggestions that low-MAO represents a genetic marker for a disorder such as schizophrenia with a lifetime risk of only 0.85%. To ensure that results were not artifacts from a familial, skewed distribution, the data were also analyzed after power transformation. In addition, hypotheses were tested using both the joint and conditional likelihoods to examine for possible misspecification of the model with respect to intergenerational differences. Finally, we allowed for non-Mendelian transmission probabilities to provide another class of alternatives against which to test the hypothesis of a major locus. All these approaches provided additional confirmation for the presence of a major locus segregating within these families.

Alleles↗
PubMed2003

Chromosomal location of a race-specific resistance gene to Mycosphaerella graminicola in the spring wheat ST6.

Septoria tritici blotch, caused by Mycosphaerella graminicola, is a serious foliar disease of wheat worldwide. Qualitative, race-specific resistance sources have been identified and utilized for resistant cultivar development. However, septoria tritici blotch resistant varieties have succumbed to changes in virulence of M. graminicola on at least three continents. The use of resistance gene pyramids may slow or prevent the breakdown of resistance. A clear understanding of the genetics of resistance and the identification of linked PCR-based markers will facilitate the recovery of wheat lines carrying multiple septoria tritici blotch resistance genes. The resistance gene in ST6 to isolate MG2 of M. graminicola was mapped with microsatellite markers in two populations, ST6/Erik and ST6/Katepwa. Bulk segregant analysis identified a marker on chromosome 4AL putatively linked to the resistance gene. A large linkage group was identified in each population using additional microsatellite markers mapping to chromosome 4AL. The resistance gene in ST6 mapped to the distal end of chromosome 4AL in each mapping population and was designated Stb7. Three of the microsatellite loci, Xwmc313, Xwmc219 and Xgwm160, mapped within 3.5 cM of Stb7; however, none flanked Stb7. Xwmc313 was the closest and mapped 0.3 and 0.5 cM from Stb7 in the crosses ST6/Katepwa and ST6/Erik, respectively. WMC313 will be very useful for marker-assisted selection of Stb7 in Canadian breeding programs because the ST6 allele of Xwmc313 was not identified in any of the Canadian common wheat cultivars tested.

Ascomycota↗