Genetic determination of head-size-related anthropometric traits in an ethnically homogeneous sample of 373 Indian pedigrees of West Bengal

The substantial involvement of genetic factors in the determination of head-size and head-shape traits has been firmly established. However, there has been a lack of agreement on a number of specific issues concerning the pattern of inheritance of craniofacial features. In this study we examined some of these issues in a large, ethnically homogeneous sample of Indian pedigrees. The data included 1,263 individuals belonging to 373 nuclear families. Eleven raw head-size traits and two synthetic phenotypes, interpreted as horizontal and vertical head-size components (HOC and VEC, respectively), were used in the analysis. To establish the pattern of inheritance of head traits, we carried out univariate and bivariate analyses. Maximum heritability estimates ranged from 0.41 to 0.83 for the studied head-size phenotypes. The portion of the total residual variance attributable to putative additive genetic factors was 68.3% and 70.3% for HOC and VEC, respectively, and common familial factor effects were found to be nonsignificant. The extent of genetic influences did not differ significantly with respect to sex or between HOC and VEC. The results of bivariate variance decomposition analysis strongly suggest the existence of common genetic factors simultaneously affecting HOC and VEC; 41.8% of the two traits' total residual variance was attributable to the effect of these common genetic factors.     

Hypertension and sodium-lithium countertransport in Utah pedigrees: evidence for major-locus inheritance.

Likelihood analysis was used to test for evidence that an allele at a major locus elevates rates of sodium-lithium countertransport (SLC) in a sample of 1,989 members of 89 Utah pedigrees. The pedigrees were ascertained through two or three sibs who died of stroke before age 74 years (stroke pedigrees), through hypertensive and normotensive probands of the Salt Lake Center of the Hypertension Detection and Followup Program (HDFP pedigrees), or through men who suffered a myocardial infarction before age 55 years (coronary pedigrees). Major-locus inheritance could be rejected in the total sample; transmission probability estimates of tau1 = .972, tau2 = .520, tau3 = .185 differed significantly from Mendelian transmission specified by tau1 = 1, tau2 = 1/2, tau3 = 0. However, heterogeneity between ascertainment groups was significant (chi2(18) = 40.06, P less than .01) and justified analysis within subsets of the sample. In the stroke pedigrees, evidence of major-locus inheritance was not found; polygenic heritability was estimated as .647. In the HDFP pedigrees, estimates of tau1 = .987, tau2 = .430, tau3 = .506 differed significantly from Mendelian transmission; the inferred model consisted of a mixture of two distributions incompatible with both Mendelian and environmental transmission but compatible with polygenic inheritance within distributions. In the coronary pedigrees, the hypothesis of Mendelian transmission could not be rejected. In the coronary pedigrees, the evidence supported an incompletely recessive allele with a frequency of .227 which elevated the level of SLC to a mean of .530 mmol/liter RBC/h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genotypechecker: an interactive tool for checking the inheritance consistency of genotyped pedigrees

Datapoint errors in pedigree genotype data sets are difficult to identify and adversely affect downstream genetic analyses. We present GenotypeChecker, a desktop software tool for assisting data cleansing. The application identifies likely data errors in pedigree/genotype data sets by performing an inheritance-checking algorithm for each marker across the pedigree, and highlights inconsistently inherited genotypes in an exploratory user interface. By 'masking' suspect datapoints and rechecking inheritance consistency, erroneous datapoints can be confirmed and cleansed from the data set. The software, examples and documentation are freely available at http://bioinformatics.roslin.ac.uk/genotypechecker.     

HLA and the inheritance of multiple sclerosis: linkage analysis of 72 pedigrees.

Linkage analysis of 72 pedigrees by the maximum-likelihood method provides evidence of linkage between HLA and the hypothesized multiple sclerosis susceptibility gene (MSSG) for both the dominant and recessive models of inheritance and for penetrance values ranging from 5%--65% (or higher). This MSSG, if it exists, is most likely located at 15%--20% recombination units from the HLA complex, probably on the B-D side. The analysis also shows that there is no heterogeneity in the estimates of linkage, and lod scores are not artifically inflated because of the association of multiple sclerosis (MS) with HLA-B7.     

Climatic factors in the development of radiographic hand osteoarthritis

A study was undertaken to evaluate whether various ethno-territorial samples have different characteristics of radiographic hand osteoarthritis (OA) and to evaluate whether climate is associated with differences in hand OA characteristics.The total sample included 4775 individuals (2220 males and 2555 females), belonging to 12 sub-samples, including 9 ethnic groups, from 10 geographic locations in the former USSR. Ethnicity, latitude, longitude, and climatic parameters (mean temperatures, humidity, and day length of January and July) were collected for each sample. X-rays of the left hand were obtained from each individual. Prevalence of hand OA was evaluated in four age groups (36-40, 41-45, 46-50, and 51-55 years). Using maximum likelihood estimation, the following characters were determined: the mean age of persons having 1 and 5 affected joints—A_m1 and A_m5, and the mean time in which one additional joint was affected—T_m. The difference between samples was evaluated using the χ²-test. The associations between hand OA, and climate were evaluated using Pearson’s correlations.Significant differences in OA characteristics among samples were found. Prevalence of hand OA in the age-group 46-50 showed significant association with longitude (r=0.57, p=0.05) and inter-seasonal temperature amplitude (r=0.77, p=0.0035) and significant negative association with mean temperature of January (r=−0.72, p=0.0089). Significant associations were found between longitude, the mean temperature of January, and inter-seasonal temperature amplitude and age-related hand OA parameters (A_m1 and A_m5).The present study indicates that the differences in characteristics of radiographic hand OA among samples are most likely associated with climatic variation.     

Mode of inheritance of primary metabolic traits in tomato

To evaluate components of fruit metabolic composition, we have previously metabolically phenotyped tomato (Solanum lycopersicum) introgression lines containing segmental substitutions of wild species chromosome in the genetic background of a cultivated variety. Here, we studied the hereditability of the fruit metabolome by analyzing an additional year's harvest and evaluating the metabolite profiles of lines heterozygous for the introgression (ILHs), allowing the evaluation of putative quantitative trait locus (QTL) mode of inheritance. These studies revealed that most of the metabolic QTL (174 of 332) were dominantly inherited, with relatively high proportions of additively (61 of 332) or recessively (80 of 332) inherited QTL and a negligible number displaying the characteristics of overdominant inheritance. Comparison of the mode of inheritance of QTL revealed that several metabolite pairs displayed a similar mode of inheritance of QTL at the same chromosomal loci. Evaluation of the association between morphological and metabolic traits in the ILHs revealed that this correlation was far less prominent, due to a reduced variance in the harvest index within this population. These data are discussed in the context of genomics-assisted breeding for crop improvement, with particular focus on the exploitation of wide biodiversity.     

Heritability patterns in hand osteoarthritis: the role of osteophytes

Introduction  

The objective of the present study was to assess heritability of clinical and radiographic features of hand osteoarthritis (OA) in affected patients and their siblings.     

Mode of inheritance in familial cases of primary gonadotropic deficiency

The mode of inheritance of primary gonadotropic deficiency was studied in 38 children and adolescents. 92% of this population was male with high frequencies of undescended testes (80%) and micropenis (31%). Anosmia was present in 61% of the patients aged more than 5 years and was a frequent genetic marker in the families. Inheritance was matrilineal in 18, X-linked dominant or autosomal dominant in 6. In 13 cases, the transmission was patrilineal and evoked autosomal dominant inheritance. An autosomal recessive transmission was likely in 7 patients. The data agree with the suggestion of multiple modes of inheritance of congenital gonadotropic deficiency, and clearly show the wide range of expressivity of the disorder.     

Microsatellite analysis of wheat chromosome 2D allows the reconstruction of chromosomal inheritance in pedigrees of breeding programmes

Fusarium head blight (FHB, scab) is a fungal disease of wheat and other small cereals that is found in both temperate and semi-tropical regions. FHB causes severe yield and quality losses, but the most-serious concern is the possible mycotoxin contamination of cereal food and feed. Breeding for FHB resistance by conventional selection is feasible, but tedious and expensive. This study was conducted to identify and map DNA markers associated with FHB resistance genes in wheat. A population of 364 F₁-derived doubled-haploid (DH) lines from the cross ’CM-82036’ (resistant)/’Remus’ (susceptible) was evaluated for Type II resistance (spread within the spike) during 2 years under field conditions. Marker analysis was performed on 239 randomly chosen DH lines. Different marker types were applied, with an emphasis on AFLP and SSR markers. Analysis of variance, as well as simple and composite interval mapping, were applied. Three genomic regions were found significantly associated with FHB resistance. The most-prominent effect was detected on the short arm of chromosome 3B, explaining up to 60% of the phenotypic variance for Type II FHB resistance. A further QTL was located on chromosome 5A and a third one on 1B. The QTL regions on 3B and 5A were tagged with flanking SSR markers, the 1B QTL was found associated with the high-molecular-weight glutenin locus. These results indicate that FHB resistance is under control of a few major QTLs operating together with unknown numbers of minor genes. Marker-assisted selection for these major QTLs involved in FHB resistance appears feasible and should accelerate the development of resistant and agronomically improved wheat cultivars. Received: 25 January 2001 / Accepted: 18 February 2001     

Number and mode of inheritance of QTL influencing backfat thickness on SSC2p in Sino-European pig pedigrees

Background

In the pig, multiple QTL associated with growth and fatness traits have been mapped to chromosome 2 (SSC2) and among these, at least one shows paternal expression due to the IGF2-intron3-G3072A substitution. Previously published results on the position and imprinting status of this QTL disagree between analyses from French and Dutch F2 crossbred pig populations obtained with the same breeds (Meishan crossed with Large White or Landrace).

Methods

To study the role of paternal and maternal alleles at the IGF2 locus and to test the hypothesis of a second QTL affecting backfat thickness on the short arm of SSC2 (SSC2p), a QTL mapping analysis was carried out on a combined pedigree including both the French and Dutch F2 populations, on the progeny of F1 males that were heterozygous (A/G) and homozygous (G/G) at the IGF2 locus. Simulations were performed to clarify the relations between the two QTL and to understand to what extent they can explain the discrepancies previously reported.

Results

The QTL analyses showed the segregation of at least two QTL on chromosome 2 in both pedigrees, i.e. the IGF2 locus and a second QTL segregating at least in the G/G F1 males and located between positions 30 and 51 cM. Statistical analyses highlighted that the maternally inherited allele at the IGF2 locus had a significant effect but simulation studies showed that this is probably a spurious effect due to the segregation of the second QTL.

Conclusions

Our results show that two QTL on SSC2p affect backfat thickness. Differences in the pedigree structures and in the number of heterozygous females at the IGF2 locus result in different imprinting statuses in the two pedigrees studied. The spurious effect observed when a maternally allele is present at the IGF2 locus, is in fact due to the presence of a second closely located QTL. This work confirms that pig chromosome 2 is a major region associated with fattening traits.     

Mode of serotype inheritance in exoconjugant progeny of the ciliate Dileptus anser

Two clones of Dileptus anser, originally isolated from natural reservoirs and referred to below as B and D clones, were found to display different serotypes, when cultured under identical laboratory conditions. On being tested with two different polyclonal rabbit immune sera against each particular clone (the classic immobilization test) these clones showed no cross-reaction. At a standard dilution (1:50) and at a standard exposure time (4 h), either of the two immune sera immobilized 100% or commonly 0% of homologous and heterologous clone cells, respectively. In addition, the difference in serotypes was confirmed by the immunofluorescence analysis. By crossing (conjugation) between B (mating type I) and D (mating type III) cells, exconjugant F1 clones were obtained. Their serotypes were then tested (the same immobilization test) with antisera against both the "parental" clones: some clones were tested before their sexual maturation in ca. one month after conjugation, while others were examined in approximately 4 months after conjugation, i.e. after reaching maturity. Each of the F1 clones could react with both immune sera, which means that they possessed the intermediate, "hybrid" phenotype. Five different F1 clones were selected, and each of them was back-crossed to both "parental" clones, B and D. We succeeded in raising 25 exconjugant F2 (B1, to be more exact) clones from F1 x B crosses and 26 clones from F1 x D crosses. The conventional testing of these clones in 5-10 weeks after conjugation provided quite unexpected results, since among them no segregation for "parental" serotypes was observed. Each of the 51 tested clones demonstrated the "hybrid" serotype--seemingly the same as that of F1 clones. Such a non-Mendelian inheritance of the character is hardly to explain from the standard, canonical assumptions on the genetic control of serotype difference between original "parental" clones (different alleles in one locus? different loci?). Also it does not seem likely that the absence of segregation could result from differential survival of various phenotypes in F2 (although the total viability of exconjugant clones appeared rather low). The above data obviously need further confirmations and experimental analyses. We attempt to discuss the obtained results in terms of the epigene hypothesis (Tchuraev, 1975) and in relation to the epigenetic control of serotype expression in species of the Paramecium aurelia complex and in Tetrahymena thermophila, which are "the chosen few" subjects in ciliate genetics.     

Climate is associated with prevalence and severity of radiographic hand osteoarthritis

The aim of this study was to evaluate whether geographic location and climatic factors are associated with prevalence and severity of radiographic hand osteoarthritis (OA) in several samples of the same ethnicity.The total sample included 2079 ethnic Russians (900 males and 1179 females), belonging to 7 samples from different geographic locations in the former USSR. Places of residence were characterized by latitude, longitude, altitude and climatic parameters (mean temperatures, humidity, and daylight duration of January and July). Radiographs of the left hand were obtained from each individual. Osteoarthritis (OA) was evaluated in 14 hand joints according to Kellgren and Lawrence's grading system. OA was characterized by the presence of at least one affected joint and its severity by the number of affected joints (NAJ). Statistical analysis included prevalence estimation, polynomial and logistic regressions, ANOVA and correlation analyses.Prevalence of hand OA and NAJ were significantly associated with latitude and altitude and with most climatic parameters (except the inter-seasonal temperature amplitude and the mean atmospheric pressure of January and July). The highest correlations of hand OA prevalence were found with altitude (r = 0.29, p < 0.001), annual precipitation (r = −0.26, p < 0.001) and the mean temperatures of July (r = 0.26, p < 0.001). The highest correlations of NAJ were found with altitude (r = 0.51, p < 0.001), mean humidity in January (r = −0.44, p < 0.001) and the mean day duration in January (r = 0.0.37, p < 0.001).The present study demonstrates that the differences in prevalence and severity of radiographic hand OA among Russian samples are most likely dependent on climatic conditions in the place of residence.     

Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3

Osteoarthritis (OA) is the most common human joint disease, characterized by loss and/or remodeling of joint synovium, cartilage, and bone. Here, we describe a genomewide linkage analysis of patients with idiopathic hand OA who were carefully phenotyped for involvement of either or both the distal interphalangeal (DIP) joints and the first carpometacarpal (CMC1) joints. The best linkage peaks were on chromosomes 4q and 3p and on the short arm of chromosome 2. Genomewide significance was reached for a locus on chromosome 2 for patients with affected CMC1 joints (LOD = 4.97); this locus was also significant for patients with OA in both CMC1 and DIP joints (LOD = 4.44). The peak LOD score at this locus coincides with a gene, MATN3, encoding the noncollagenous cartilage extracellular matrix protein, matrilin-3. Subsequent screening of the genomic sequence revealed a missense mutation, of a conserved amino acid codon, changing threonine to methionine in the epidermal growth factor-like domain in matrilin-3. The missense mutation cosegregates with hand OA in several families. The mutation frequency is slightly more than 2% in patients with hand OA in the Icelandic population and has a relative risk of 2.1.     

Adiposity and hand osteoarthritis: the Netherlands Epidemiology of Obesity study

Introduction

Obesity, usually characterized by the body mass index (BMI), is a risk factor for hand osteoarthritis (OA). We investigated whether adipose tissue and abdominal fat distribution are associated with hand OA.

Methods

The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45 to 65 years, including 5315 participants (53% women, median BMI 29.9 kg/m²). Fat percentage and fat mass (FM) (kg) were estimated using bioelectrical impedance analysis. The waist-to-hip ratio (WHR) was calculated. In 1721 participants, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (cm²) were assessed using abdominal MR imaging. Hand OA was defined according to the ACR criteria.Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of fat percentage, FM, WHR, VAT and SAT with hand OA using logistic regression analyses per standard deviation, stratified by sex and adjusted for age.

Results

Hand OA was present in 8% of men and 20% of women. Fat percentage was associated with hand OA in men (OR 1.34 (95% CI 1.11 to 1.61)) and women (OR 1.26 (1.05 to 1.51)), as was FM. WHR was associated with hand OA in men (OR 1.45 (1.13 to 1.85)), and to a lesser extent in women (OR 1.17 (1.00 to 1.36)). Subgroup analysis revealed that VAT was associated with hand OA in men (OR1.33 (1.01 to 1.75)). This association increased after additional adjustment for FM (OR 1.51 (1.13 to 2.03)).

Conclusions

Fat percentage, FM and WHR were associated with hand OA. VAT was associated with hand OA in men, suggesting involvement of visceral fat in hand OA.     

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38–0.94 and OR = 0.59, 95% CI = 0.38–0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99–3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25–1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08–0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29–5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.     

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38-0.94 and OR = 0.59, 95% CI = 0.38-0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99-3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25-1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08-0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29-5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.     

Mode of inheritance of azinphosmethyl resistance in a laboratory-selected strain of Trioxys pallidus

Homogeneity in azinphosmethyl resistance was assessed in males of a laboratory-selected (Select-17) and susceptible (Yolo) colony of Trioxys pallidus Haliday (Hymenoptera: Aphidiidae) using a time response assay. No evidence of heterogeneity within the two colonies was found. Reciprocal crosses between the Yolo and the Select-19 (the Select-17 colony following two additional selections) colonies resulted in F₁ females that exhibited a semidominant response to azinphosmethyl with a dominance value (D) of 0.32, as well as no evidence of maternal effects or sex linkage. Responses of F₂ progeny to azinphosmethyl suggest that more than one gene may be involved because no inflection was observed in the time response lines of F₂ males. Additional research is required to fully elucidate the mode of inheritance.     

Minimum-recombinant haplotyping in pedigrees

This article presents a six-rule algorithm for the reconstruction of multiple minimum-recombinant haplotype configurations in pedigrees. The algorithm has three major features: First, it allows exhaustive search of all possible haplotype configurations under the criterion that there are minimum recombinants between markers. Second, its computational requirement is on the order of O(J(2)L(3)) in current implementation, where J is the family size and L is the number of marker loci under analysis. Third, it applies to various pedigree structures, with and without consanguinity relationship, and allows missing alleles to be imputed, during the haplotyping process, from their identical-by-descent copies. Haplotyping examples are provided using both published and simulated data sets.