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PubMed1993

Exploring the HDL likelihood surface.

Using random initial parameter estimates, three segregation analysis models of the inheritance of HDL2 in the Berkeley GAW8 data set were maximized 5000 times each. Initial parameter estimates were assumed to be uniformly distributed on intervals formed by parameter boundaries. The three models were unrestricted, environmental, and Mendelian regressive type A models. Likelihood ratio tests of the global maxima rejected the Mendelian model and accepted the environmental model. However, tests using local maxima accepted the Mendelian model and both rejected and accepted the environmental model. Patterns among the initial parameter estimates of convergent runs were examined to develop empirical rules to increase the frequency of convergence. These rules were tested using data on apoAI in the Berkeley GAW8 data set.

Genetic Predisposition to Disease↗
PubMed1993

Influence of genotype-dependent effects of covariates on the outcome of segregation analysis of the body mass index.

Several recent studies of the body mass index (BMI) have provided support for a recessive major gene influencing heaviness in humans. Segregation analysis of the BMI was carried out recently in a series of randomly sampled French-Canadian families to determine whether we could replicate the major gene finding by using a residual phenotype adjusted for the effects of age and sex. The best model included a recessive major effect for high BMI values with residual familial resemblance; however, Mendelian transmission could not be confirmed, and the no-transmission hypothesis (where all the tau's are constrained to be equal) was not rejected. Considering that the BMI is a complex phenotype affected by many factors and that there are known variations in body composition during growth and aging, we undertook a reanalysis of the data, using a model that allowed the estimation of genotype-specific age and gender effects. New tests on the transmission parameters satisfy the criteria for interfering Mendelian segregation. The results suggest that individuals with the "high" recessive genotype show the greatest degree of heaviness at birth, with a subsequent trend toward lower values throughout life, while individuals with the dominant "normal" genotypes show no appreciable trends with age. In addition, the "high" genotype appears to confer a greater degree of heaviness in females as compared with males. These results, along with other observations from the data, suggest that, while a recessive single gene influence may be discernible, the phenotypic expression of the BMI is likely to be complicated by genotype x environment interactions and, possibly, by the action of other loci. Further, the data also are consistent with the hypothesis that modifying factors may include the adoption of a more prudent life-style by individuals genetically predisposed to heaviness and a secular increase in the incidence, prevalence, and potency of environmentally based triggers leading to a higher penetrance of the "heavy" genotype in the young.

Adolescent↗
PubMedDate not supplied

Inheritance pattern of RAPD markers in Melipona quadrifasciata (Hymenoptera: Apidae, Meliponinae).

Melipona quadrifasciata is an important pollinator agent in several regions of Brazil. Data concerning the genetics of this species are scarce in the literature. In this work we used the random amplified polymorphic DNA (RAPD) technique to determine the degree of polymorphism and the inheritance pattern of these molecular markers in this species. Our ultimate goal is to establish tools to be used in the study of the genomic organization of M. quadrifasciata. Genomic DNA from progenies F(1) and BC(1) were assayed with 79 different primers, yielding an average of 6.67 bands and 1.68 polymorphisms per primer. Three types of polymorphisms were detected: band presence/absence, band intensity, and fragment-length polymorphisms. Most of the observed polymorphisms were band presence/absence, typical of RAPD-dominant markers. The number of observed polymorphisms and their segregation in accordance with a Mendelian proportion confirm the importance of this technique for genome analysis of species like M. quadrifasciata that are poorly studied at the genetic level.

Animals↗
PubMed1994

The number of genotypic assignments on a genealogy. I. The method and simple examples.

This paper demonstrates how the number of possible genotypic assignments consistent with the rules of Mendelian genetics and with any known phenotypes can be calculated for an arbitrary genealogy. This is of interest both in the contest of the uses of the Metropolis algorithm for pedigree analysis and in its own right. Bounds on the number of states for certain regular and random genealogies are also obtained, and further results will be given in a later paper.

Algorithms↗
PubMed1994

Linkage mapping in diploid alfalfa (Medicago sativa).

A genome map of cultivated alfalfa was constructed using segregating restriction fragment length polymorphisms (RFLPs) and random amplified polymorphic DNAs (RAPDs) in a diploid backcross population generated from noninbred parents. Among the 153 loci scored in 87 progeny, four segregation ratios were observed for codominant and dominant markers: 1:1, 1:2:1, 1:1:1:1, and 3:1. Deviations from expected Mendelian ratios (p < 0.05) were observed for 34% of the loci studied. A genome map was assembled from two separate linkage maps, each constructed from a subset of the segregation data. One linkage map was constructed from 46 RFLP and 40 RAPD markers segregating 1:1 from the F1 parent of the backcross and the other linkage map was constructed from 33 RFLP and 28 RAPD markers segregating 1:1 from the recurrent parent. Sixteen loci with alleles segregating 1:1 from both parents were used as locus bridges to align individual linkage groups between the two maps. The combined use of RFLPs and RAPDs was an effective method for developing an alfalfa genome map.

Alleles↗
PubMed1996

[Pedigree investigation of familial non-insulin dependent diabetes mellitus].

UNLABELLED: To discuss the inheritant mode of familial NIDDM. METHODS: According to WHO criteria of DM, 100 NIDDM Probands with family history of DM were diagnosed and 100 persons were chosen at random for controls. The survey of DM was performed in both groups, including FBG, HbAlc, FINS. Some members had insulin release test. RESULTS: The prevalance rates of DM in familial DM group were 26 times of the control group (34.3% and 1.3%). The prevalance rate of DM among first-degree relation was 18 times higher than that in general population (28.3% and 1.5%). The rate of diabetes in the siblings and in the off-springs was 44.4% and 9.7% respectively. The pedigree analyses showed that 83.9% affected families had one diabetic parent, one half siblings had DM, and there was a successive transmission of DM through at least three generations in sixteen large families. Besides, the incidence of DM was much higher in females than in males (40% and 28%). Among affected parents, diabetlic mothers were much more than diabetic fathers (50.8% and 27.6% P < 0.01). CONCLUSION: Familial NIDDM had a familial aggregation. It was inherited in the manner of Mendelian autosomal dominant inheritance. The difference between the rate in DM mothers and fathers was probably due to unequal prevalance rate in females and males.

Adult↗
PubMed2004

Meiotic recombination hot spots and human DNA diversity.

Meiotic recombination plays a key role in the maintenance of sequence diversity in the human genome. However, little is known about the fine-scale distribution and processes of recombination in human chromosomes, or how these impact on patterns of human diversity. We have therefore developed sperm typing systems that allow human recombination to be analysed at very high resolution. The emerging picture is that human crossovers are far from randomly distributed but instead are targeted into very narrow hot spots that can profoundly influence patterns of haplotype diversity in the human genome. These hot spots provide fundamental information on processes of human crossover and gene conversion, as well as evidence that they can violate basic rules of Mendelian inheritance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1984

Lipoprotein genes and hyperlipidemia.

The hyperlipidemias, with hypertension, diabetes mellitus and cigarette smoking, are amongst the major risk factors for the development of atheroma. The inter-relationships of hyperlipidemia and atheroma are complex but both appear to have a strong inherited component. Amongst the multiple genetic factors determining the common forms of hyperlipidemia, the apolipoprotein genes coding for the major peptides of the plasma lipoproteins (chylomicrons, VLDL, LDL and HDL) may be of particular relevance since the latter form a system of inter-converting particles for the delivery of lipid (triglyceride and cholesterol) to peripheral tissues (including the arterial wall). Recently several apolipoprotein genes have been isolated. Particularly interesting results have been obtained with the apolipoprotein AI and CIII genes. The DNA sequence of both genes and their immediate flanking region was determined. The two genes are physically linked and convergently transcribed. The cloning of the apolipoprotein genes made possible a detailed genetic study of patients with defects in lipid metabolism. An altered apo AI gene was shown to be inherited as a Mendelian trait linked to premature atherosclerosis in an affected family. Furthermore, the alteration of the apo AI gene seems to affect the expression of the apo CIII gene. Another DNA polymorphism that generates a new SstI site was shown to be present at low frequency (8%) in a random sample of the population. However, its frequency increased dramatically (42%) in a group of hypertriglyceridemic patients. It is thus not inconceivable that further studies of the genes involved in lipid metabolism will eventually help to replace the present phenotype based classification of lipid metabolism disorders by a genotype based system.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed2000

Genetic differences in the frequency of the hinge variants of porcine IgA is breed dependent.

The distribution of the IgA(a) and IgA(b) alleles of porcine IgA in over 160 randomly-selected animals revealed an abundance of heterozygotes but only two b/b homozygotes. Since the IgA(b) allotype is a splice site mutant lacking two-thirds of the hinge, this study tests the hypothesis that pigs with this genotype may be at a selective disadvantage while heterozygous individuals may be at some advantage. This hypothesis was tested by collecting data on 374 animals of known breed and often parentage. We show here that when breed was not considered, young animals of known parentage had genotypic frequencies identical to that expected for Mendelian alleles but that a/b heterozygotes were overrepresented in adults. However, when analyzed with regard to breed, a very strong association between breed and the frequency of the IgA(a) and IgA(b) alleles was discovered. Meishan and NIH minipigs were homozygous for IgA while heterozygotes predominated in Berkshire, Chester White, Durocs, Hampshire and Landrace. Animals homozygous for IgA(b) were best represented in the White Cross line. We show here that this very strong breed dependency of IgA allotypy in swine can produce a sample bias that can explain why only two b/b homozygotes (1.3%) were found in the 160 randomly-selected samples since the original samples came from primarily Landrace and Yorkshire animals. The expected frequency of b/b homozygotes in these breeds would be <3%. Thus, the data presented here reject the hypothesis that swine homozygous for a trait that results in loss of two-thirds of the IgA hinge, are selected against and that heterozygotes are positively selected. Rather, the study shows that IgA(a) and IgA(b) appear to be simple, breed-dependent allotypic markers.

Alleles↗
PubMed1972

The random phenotype concept, with applications.

A random phenotype is defined as a probability distribution over any given set of phenotypes. This includes as special cases the kinds of phenotypes usually considered (qualitative, quantitative, and threshold characters) and all others. Correspondingly general methods are indicated for analyzing data of all forms in terms of the classical Mendelian factor concept (as distinct from the biometrical methods usually applied to measurement and graded data, associated with the effective factor concept). These are applied in a new analysis of the data of E. L. Green (1951, 1954, 1962) on skeletal variation in the mouse. The adequacies of various classical one-factor and several-factor models are considered. Indications of an underlying scale are found from this new standpoint. The results are compared with those obtained by Green using the scaling approach. An illustrative application is also made to some of Bruell's (1962) continuous behavioural data on mice. This work was substantially completed in 1959 but not previously prepared for publication. The same approach was originated and developed independently by R. L. Collins who has treated a wider range of theoretical problems (cf. Collins 1967, 1968a, 1969b, 1970c) and a wider range of applications (cf. Collins and Fuller 1968; Collins 1968b, 1969a, 1970a). A less general independent development is that of Mode and Gasser 1972.

Animals↗
PubMed1989

Gene conversion as a possible factor influencing genetic polymorphism.

The ostracode Cytherissa lacustris (Sars) has been obligatorily parthenogenetic at least since the Mesopleistocene. Old and large populations of it from the lakes of the Salzkammergut area in Austria exhibit quite high polymorphism and quasi-Mendelian proportions at the locus coding for glucose-6-phosphate isomerase. It is argued that this polymorphism has been attained through generations owing to gene conversion operating on the basis of the founder effect, mutations and migration; the effects of gene conversion were then amplified by selection and/or by random events.

Electrophoresis, Starch Gel↗
PubMed1997

Mating-type loci segregate aberrantly in Phytophthora infestans but normally in Phytophthora parasitica: implications for models of mating-type determination.

In the oomycete, Phytophthora infestans, mating type is determined by a locus that segregates in a non-Mendelian manner consistent with its linkage to a system of balanced lethals. The significance of this unusual phenomenon was addressed by studying the segregation patterns of DNA markers linked to mating type in the related species, P. parasitica. This was done using loci identified by either RAPD analysis of P. parasitica crosses or by cross-hybridization with RFLP markers linked to mating type in P. infestans. The resulting data revealed that, unlike P. infestans, mating type in P. parasitica was regulated by a locus displaying Mendelian segregation. An improved model for mating-type determination in Phytophthora is presented.

Chromosome Mapping↗
PubMed1993

Highly polymorphic tetramer repeat (GATA)n on human chromosome 11p15.3.

A tetrameric repeat sequence (GATA)n was identified by random DNA sequencing of chromosome 11-specific cosmid clones and located at 11p15.3 by fluorescence in situ hybridization. Oligonucleotide primers flanking the repetitive unit were used to amplify the DNA using the polymerase chain reaction (PCR) and this repetitive element was shown to be highly polymorphic and inherited in typical Mendelian fashion. Analysis of amplification products containing the repetitive element from 45 unrelated Caucasian individuals and five families showed at least five alleles at this locus, ranging from 227 to 249 bases in length. This polymorphism may serve as a useful PCR-detectable genetic marker for 11p15.3, a landmark for disease gene isolation, and a locus for identity testing.

Alleles↗
PubMed1999

An apparent excess of sex- and reproduction-related genes on the human X chromosome.

We describe here the results of a search of Mendelian inheritance in man, GENDIAG and other sources which suggest that, in comparison with autosomes 1, 2, 3, 4 and 11, the X chromosome may contain a significantly higher number of sex- and reproduction-related (SRR) genes. A similar comparison between X-linked entries and a subset of randomly chosen entries from the remaining autosomes also indicates an excess of genes on the X chromosome with one or more mutations affecting sex determination (e.g. DAX1), sexual differentiation (e.g. androgen receptor) or reproduction (e.g. POF1). A possible reason for disproportionate occurrence of such genes on the X chromosome could be that, during evolution, the 'choice' of a particular pair of homomorphic chromosomes for specialization as sex chromosomes may be related to the number of such genes initially present in it or, since sex determination and sexual dimorphism are often gene dose-dependent processes, the number of such genes necessary to be regulated in a dose-dependent manner. Further analysis of these data shows that XAR, the region which has been added on to the short arm of the X chromosome subsequent to eutherian-marsupial divergence, has nearly as high a proportion of SRR genes as XCR, the conserved region of the X chromosome. These observations are consistent with current hypotheses on the evolution of sexually antagonistic traits on sex chromosomes and suggest that both XCR and XAR may have accumulated SRR traits relatively rapidly because of X linkage.

Databases, Factual↗
PubMed1990

Congenital heart disease: incidence and inheritance.

Congenital heart disease occurs in approximately 1 per cent of liveborn children, but in a much higher percentage of those aborted spontaneously or stillborn. To detect as many as possible with CHD, including those with mild lesions, very intensive studies are needed. Studies that are not so intensive, especially those done before modern diagnostic techniques were in general use, considerably underestimated the incidence of CHD in liveborn children. It appears that the incidence of CHD and of the various individual lesions does not differ in different countries or at different times, providing the ascertainment of CHD is complete and accurate. The commonest form of CHD is the ventricular septal defect, which occurs in 30 to 40 per cent of all children with CHD. The risks of recurrence in siblings and of transmission to future generations depends on the exact mode of inheritance involved. Approximately 5 to 8 per cent of CHD is due to gross chromosomal abnormalities, and the recurrence risk is that of the chromosomal derangement itself. Because many children with these chromosomal lesions die in infancy or have reduced fertility, the risk to future generations is relatively low. About 3 per cent of CHD is due to classical Mendelian gene effects, with correspondingly high recurrence risks in first-degree relatives. Most CHD has lower risks of recurrence and transmission than those predicted by Mendelian single-gene action. The popular explanation for their inheritance has been the interaction of polygenic effects and the environment, but recent studies of the recurrence and transmission risks of various forms of CHD do not fit this model well. The alternative model is a single gene defect modulated by random events. The recurrence risks for future siblings are 2 to 6 per cent, and for offspring are 1 to 10 per cent, but in a few families the recurrence and transmission risks may be much higher.

Chromosome Aberrations↗
PubMed1985

The inheritance of enzyme variants of glutamic-oxaloacetic transaminase in Paragonimus ohirai.

Lung flukes, Paragonimus ohirai, from Kinosaki, Japan, characterized by 3 electrophoretic variants, FF, FS and SS, of glutamic-oxaloacetic transaminase (GOT: EC 2.6.1.1) were crossed in the laboratory. In the case of a cross between FS and SS, a parent, FS, produced 9 SS and 16 FS clones in the offspring, numbers not significantly different from that expected (1:1) from Mendelian inheritance. From the other cross FS X FF, 20 clones originating from the respective 20 miracidia were obtained from a parent FS. The phenotype segregation ratio was 6 FF and 14 FS, which is not significantly different from Mendelian inheritance expectation. Only 3 clones were obtained from the other parent FF, but these segregated in a ratio of 2 FS: 1 FF. These breeding data indicate that the GOT isozymes of P. ohirai are controlled by 2 codominant alleles, GotF and GotS at a single locus whose products aggregate randomly, forming a dimer.

Animals↗
PubMed2003

The hairless (hr) gene is involved in the congenital hypotrichosis of Valle del Belice sheep.

Congenital hypotrichosis in mammalian species consists of partial or complete absence of hair at birth. The hairless gene is often responsible for this disorder in men, mice and rats. Recent experimental data on Valle del Belice sheep reared in Sicily for milk production, support the genetic control of the ovine hypotrichosis as a Mendelian recessive trait. The ovine hairless gene was chosen as the candidate gene involved in this disorder. Blood samples were collected from Valle del Belice sheep with the normal and hypotrichotic phenotypes. Almost the entire hairless gene was successfully amplified using the long PCR technique. Unrelated sheep with differing phenotypes were randomly chosen for sequencing the amplified products. Different mutations related to the hypotrichotic phenotype were found in exon 3. In fact, sequencing revealed an A/T transversion at position 739, a G/A transition at position 823, and a C/T transition at position 1312. From these nucleotide exchanges, three substitutions of the processed mature protein were deduced at the amino acid positions 247 (Thr/Ser), 275 (Ala/Thr), and 438 (Gln/Stop). A PCR-SSCP based test was developed in order to detect the last mutation, which is responsible for the hypotrichotic phenotype.

Animals↗
PubMed1995

Inheritance of RAPD markers in the guppy fish, Poecilia reticulata.

Random Amplified Polymorphic DNA (RAPD) fingerprinting offers a rapid and efficient method for generating a new series of DNA markers in fishes. Three oligonucleotide primers (two 10-mers and one 9-mer) and their paired combinations were found to generate different but reproducible RAPD fingerprints in the guppy. Of these, a 10-mer primer (designated S3D2) was used to detect DNA polymorphisms in two guppy varieties, Green Snakeskin (GSS) and 3/4Black (3/4B). High Genetic Similarity (SI) was found among individuals of the GSS and 3/4B varieties indicating low intra-variety genetic variability. The average SI values for the Green Snakeskin and 3/4Black varieties were 0.78 +/- 0.104 and 0.81 +/- 0.083, respectively. The average SI value between individuals of the GSS and 3/4B varieties was 0.66 +/- 0.066, indicating higher genetic variability between the two varieties. To study the inheritance of RAPD markers, single-pair crosses were set up between males of the GSS variety and females of the 3/4B variety. The S3D2 primer was used to generate RAPD fingerprints of the parents and their F1 offsprings. A total of 14 RAPD markers were scored from these crosses. Of these markers, eight (60.0%) of them were polymorphic. The RAPD markers were shown by the F1 to exhibit dominant Mendelian inheritance and could thus be used for subsequent genetic linkage mapping of the guppy.

Animals↗