Refsum's disease (heredopathia atactica polyneuritiformis)

The formal genetics of 37 patients suffering from Refsum's disease is reviewed. The absence of the disease in parents and relatives excepts sibs of the propositi, the high parental consanguinity rate, and the observed number of affected sibs are in agreement with the assumption of an inheritance by a rare autosomal recessive gene. The geographical distribution of the patients suggests that most of them may have originated from one Scandinavian stock.     

Power evaluations for family-based tests of association with incomplete parental genotypes

While a variety of methods have been developed to deal with incomplete parental genotype information in family-based association tests, sampling design issues with incomplete parental genotype data still have not received much attention. In this article, we present simulation studies with four genetic models and various sampling designs and evaluate power in family-based association studies. Efficiency depends heavily on disease prevalence. With rare diseases, sampling affecteds and their parents is preferred, and three sibs will be required to have close power if parents are unavailable. With more common diseases, sampling affecteds and two sibs will generally be more efficient than trios. When parents are unavailable, siblings need not be phenotyped if the disease is rare, but a loss of power will result with common diseases. Finally, for a class of complex traits where other genetic and environmental factors also cause phenotypic correlation among siblings, little loss of efficiency occurs to rare disease, but substantial loss of efficiency occurs to common disease.     

Two sibs with duplication of 4q31-->qter due to 3:1 meiotic disjunction and mild phenotype

Two sibs with duplication of 4q31-->qter due to 3:1 meiotic disjunction and mild phenotype: Clinical and cytogenetic findings in two sibs with partial duplication of 4q31.3-->qter and 21q11.2-->pter are reported. These patients are rare cases of reoccurrence of those partial trisomies due to 3:1 segregation of a maternal balanced translocation. A review of the literature reporting cases of trisomy of the 4q31-->qter segment is also made; previously reported cases mostly in addition have deletions of other chromosomes resulting from adjacent segregation of balanced translocation. The findings of our study confirm the high risk for offspring with unbalanced rearrangements in women with reciprocal translocation involving acrocentric and short chromosome segments. The study also points out that duplication of 4q31-->qter may go along with only mild phenotypic findings if there is no significant additional aneuploidy of the other chromosome involved in the rearrangement.     

Morphological properties ofSchizosaccharomyces pombe in a continuous culture

The dilution rate (specific growth rate) influences the mean volume ofS. pombe cells and their length—width ratio. The degree of asymmetry of the cell division is also a function of the dilution rare. The difference between the volume and length of both sibs of the dividing cell is significant under conditions of substrate limitation, whereas with excess substrate both parts of the cell are identical in volume.     

Kin selection and coefficients of relatedness in family-structured populations with inbreeding

We consider family specific fitnesses that depend on mixed strategies of two basic phenotypes or behaviours. Pairwise interactions are assumed, but they are restricted to occur between sibs. To study the change in frequency of a rare mutant allele, we consider two different forms of weak selection, one applied through small differences in genotypic values determining individual mixed strategies, the other through small differences in viabilities according to the behaviours chosen by interacting sibs. Under these two specific forms of weak selection, we deduce conditions for initial increase in frequency of a rare mutant allele for autosomal genes in the partial selfing model as well as autosomal and sex-linked genes in the partial sib-mating model with selection before mating or selection after mating. With small differences in mixed strategies, we show that conditions for protection of a mutant allele are tantamount to conditions for initial increase in frequency obtained in additive kin selection models. With particular reference to altruism versus selfishness, we provide explicit ranges of values for the selfing or sib-mating rate based on a fixed cost-benefit ratio and the dominance scheme that allow the spreading of a rare mutant allele into the population. This study confirms that more inbreeding does not necessarily promote the evolution of altruism. Under the hypothesis of small differences in viabilities, the situation is much more intricate unless an additive model is assumed. In general however, conditions for initial increase in frequency of a mutant allele can be obtained in terms of fitness effects that depend on the genotypes of interacting individuals or their mates and generalized conditional coefficients of relatedness according to the inbreeding condition of the interacting individuals.     

Mapping quantitative-trait loci in humans by use of extreme concordant sib pairs: selected sampling by parental phenotypes.

In two previous articles, we have considered sample sizes required to detect linkage for mapping quantitative-trait loci in humans, using extreme discordant sib pairs. Here, we examine further the use of extreme concordant sib pairs but consider the effect of parents' phenotypes. Sample sizes necessary to obtain a power of 80% with concordant sib pairs at a significance level of .0001 are given, stratified by parental phenotypes. When there is no residual correlation between sibs, the parental phenotypes have little impact on the sample sizes. When residual correlations between sibs exist, we show, however, that power can be considerably reduced by including extreme sib pairs when the parents also have similarly extreme values. Thus, we recommend the exclusion of such pairs from linkage studies. This recommendation reduces the required sample sizes by 3- to 28-fold. The degree of saving in the required sample sizes varies among different models and allele frequencies. The reduction is most dramatic (a 28-fold reduction) for a rare recessive gene.     

Seed provisioning within holly fruits: test of the hierarchical model

Seed provisioning within holly Ilex aquifolium fruits was examined after a controlled pollination experiment to obtain full-sibs. The distribution of dry mass in stony endocarp and endosperm was determined according to the rank in the size hierarchy of the sibs within fruit. Resources were more equally distributed among sibs in the endocarps than in the endosperms, which might suggest sibling competition among endosperms and no evidences of competition in the tissue controlled by the maternal sporophyte. When the sibs are ranked by size, seed provisioning fit reasonably with the hierarchical model. Differences among consecutive sibs increased down the hierarchy, the second sib in the size hierarchy was less variable in resource acquisition than the others, and the disparity in the distribution of resources among sibs decreased with fruit size increases. These results seems to be in accordance with both kin selection model and hierarchical model, which indicates at the same time control of resource provisioning by the maternal plant and differences in vigour among sibs. This revised version was published online in August 2006 with corrections to the Cover Date.     

Familial dwarfism with high IR-GH: Report of two affected sibs with genetic and epidemiologic considerations

Summary Two sibs with high serum IR-GH dwarfism, born to first-cousin parents are described. Genetic analysis based upon 25 reported informative kindreds indicates that the condition has an autosomal recessive pattern of inheritance. Population evaluation and epidemiology of the affected subjects suggest that mutation rates of the gene determining the disease in non-Jewish populations could be as rare as 3.2×10^-5. However, its prevalence must be exceptionally high among endogamous Oriental Jewish groups derived from a common gene pool in historical times.     

Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report

Acro-cardio-facial syndrome (ACFS) is a rare genetic disorder characterized by split-hand/split-foot malformation (SHFM), facial anomalies, cleft lip/palate, congenital heart defect (CHD), genital anomalies, and mental retardation. Up to now, 9 patients have been described, and most of the reported cases were not surviving the first days or months of age. The spectrum of defects occurring in ACFS is wide, and both interindividual variability and clinical differences among sibs have been reported. The diagnosis is based on clinical criteria, since the genetic mechanism underlying ACFS is still unknown. The differential diagnosis includes other disorders with ectrodactyly, and clefting conditions associated with genital anomalies and heart defects. An autosomal recessive pattern of inheritance has been suggested, based on parental consanguinity and disease's recurrence in sibs in some families. The more appropriate recurrence risk of transmitting the disease for the parents of an affected child seems to be up to one in four. Management of affected patients includes treatment of cardiac, respiratory, and feeding problems by neonatal pediatricians and other specialists. Prognosis of ACFS is poor.     

A neurogenetic study in an inbred population]

A Tatar family from a semi-isolated village in the Gorky Region is described in which a neurological and ophthalmological syndrome was inherited. In homozygotes this syndrome comprised the degeneration of subcortical cerebral ganglia (hyperkinesis), nystagmus, oligophrenia and a peculiar variant of tapetoretinal degeneration. Heterozygotes exhibited ophthalmological abnormalities, such as the similar defects of eye bottom and nystagmus. The two homozygotes observed were sibs derived from a marriage between first cousins. Five more families with other rare hereditary anomalies (both dominant and recessive) were discovered in this village. The total inbreeding coefficient in the village was found to be 0.0075. The high degree of inbreeding, subisolation and high fertility are regarded as factors favorable for the distribution of rare deleterious mutations due to the founder-effect.     

ABO and Rh blood groups in relation to sex ratio, mean number and mortality of sibs.

Data are presented on the sex ratio, mean number and mortality of the sibs of 17,060 schoolchildren, and on the sex ratio and mean number of the sibs of 5,785 blood donors, in relation to the children's and donors' sex and ABO and Rh blood groups. The sex ratio is significantly higher for the sibs of AB + B than for those of A + O schoolboys, and for the sibs of Rh-negative than for those of Rh-positive male blood donors, but in both cases the mean number of sibs is exactly the same for the first-mentioned as for the second-mentioned category.     

A familial tetraphocomelia syndrome involving limb deformities,cleft lip,cleft palate,and associated anomalies —A new syndrome

Summary This paper reports a rare malformation syndrome which is observed in two sibs (brother and sister) of a family. It consists of nearly symmetric reductive defects of the limbs, flexon contractures of various joints, cleft lip and cleft palate, multiple minor abnormalities including capillary hemangioma of the forehead, hypoplastic cartilages of ears and nose, micrognathia, intrauterine growth retardation, and possibly mental retardation. Chromosomes of both parents and propositi are normal. Genetic data suggest autosomal recessive inheritance.     

A study of fluctuating dermatoglyphic asymmetry in the sibs and parents of cleft lip propositi.

Fluctuating asymmetry was studied in cleft lip propositi and their normal sibs and parents. The traits examined were a-b ridge counts and fingerprint patterns. Propositi with a family history of this congenital malformation and their normal sibs and parents were significantly different from the controls for this type of asymmetry. Propositi without a family history and their normal sibs and parents were similar to the controls. These results support the hypothesis that familial and sporadic cases of congenital cleft lip are different entities and give evidence for a genetic mechanism in the parents and sibs of the familial cases that may account for this congenital disorder and, concomitantly, increased fluctuating asymmetry.     

Empirical risk of oligophrenia in siblings of proband-oligophrenics in populations with high levels of inbreeding]

An investigation is carried out on 214 patients with oligophreny with regard to the secondary risk of the same disease for their four sibs. All patients were divided into 4 groups according to etiological symptoms, and it was found that maximal risk of the secondary disease with oligophreny was for the sibs of probably genetic group, and minimal one--for the sibs of the exogenic group. Maximal resemblance in the degree of the defect in the pair of proband-sibs was found both in probably-genetic and presumably-genetic groups. The risk of secondary oligophreny was significantly higher in sibs-probands with relatively lower degree of weak-mindedness than in those with severe mental defects. The frequency of the secondary oligophreny amond sibs of the inbred origin (18.9%) was more than twice as high (P less than 0.001) as in those of outbred origin (8.3%).     

Absence of kin discrimination in cannibalistic Anuran tadpoles of the frog Hoplobatrachus tigerinus (Daudin)

Kin discrimination was tested in the cannibalistic H. tigerinus tadpoles to know whether cannibalism is selectively directed towards non-kin members or it is indiscriminate. The association choice tests were conducted using satiated as well as starved subjects with the assumption that they will associate near non-sibs rather than near sibs with the intention of preferentially cannibalizing them. However, test tadpoles, fed or starved showed a random association choice with sibs and non-sibs, as in the end-bias stimulus blank tests. Therefore it is suggested that cannibalistic H. tigerinus tadpoles do not discriminate sibs from non-sibs and cannibalize on both rather indiscriminately.     

Are oral clefts a consequence of maternal hormone imbalance? evidence from the sex ratios of sibs of probands

BACKGROUND: The causes of oral clefts (cleft lip with or without cleft palate, CL/P, and cleft palate alone, CP) have not been established. However, maternal intrauterine hormone profiles have been suspected of being involved. There is now substantial evidence that maternal hormone concentrations around the time of conception partially control the sexes of offspring. It is possible that the hormone profiles that control sex of offspring share features of the profiles suspected of causing clefts. This can be tested by examining the sex ratios (proportions male) of the unaffected sibs of probands. If these sex ratios are skewed in the same direction as that of probands, that suggests, ex hypothesi, maternal hormonal involvement in the causation of clefts. METHODS: Accordingly, a search was made for data on the sex ratios of the unaffected sibs of probands with clefts. For reasons given in the text, this search was informal rather than based on electronic data retrieval systems. Nine papers were located giving sex ratios of sibs of probands with CL/P and CP. RESULTS: Published data suggest that the sibs of probands with CL/P have a significantly higher sex ratio than the sibs of probands with CP. Thus the sib sex ratios are skewed in the same direction as those of the probands themselves. In other words, parents (mothers) of CL/P patients apparently have a tendency to produce boys, and parents of CP patients to produce girls. CONCLUSION: Accordingly, it is suggested that maternal hormone profiles may partially explain the unusual sex ratios (of probands and their sibs), as well as the malformations.     

HLA and disease: predictions for HLA haplotype sharing in families.

An analysis of published data on the segregation of HLA haplotypes in families with more than one individual affected with insulin-dependent diabetes mellitus or multiple sclerosis yields three conclusions: (1) In families with unaffected parents, affected sib pairs are much more often HLA haplotype identical in sibships with two affected sibs than in sibships with three or four affected sibs (P less than .01). (2) In families with unaffected parents and HLA half-identical affected sibs, well siblings more often receive the single haplotype not found in the affected sibs than is expected by chance (P less than .05). (3) In families with one affected parent, well siblings of affected individuals may share with the affected child a haplotype from the unaffected parent less than 50% of the time (P less than .10). These results are consistent with the premise that in some non-Mendelian, familial, HLA-associated disease more than one gene may contribute to susceptibility to the disorder.     

The sex ratio in spina bifida

It is shown that the well known excess of females in spina bifida children is statistically significant when they are compared with (a) the general population and (b) their sibs.Although there is a small excess of males amongst the sibs this is not statistically significant when compared with the general population and when all the children in these families are considered they appear to have a sex ratio very similar to that general population. The sibs of the parents of spina bifida children show a statistically significant excess of females.These findings are discussed with particular reference to the genetics of spina bifida.     

Kartagener's syndrome in sibs: Clinical and immunologic investigations

Summary In a sibship of ten children descending from a first cousin's marriage, two sibs were affected by Kartagener's syndrome with the typical symptoms of situs inversus, bronchiectasis, and polyposis nasi. Clinical investigation of the entire family revealed chronic infections of the paranasal sinus in five sibs and the mother, two of whom had bronchiectasis as well. Immunologically, a persistent cellular or humoral defect could not be detected in any of the family members. In the HLA system, only the two sibs with Kartagener's syndrome had identical HLA types; all other family members had different combinations. A linkage between the loci for the HLA system and Kartagener's syndrome is discussed.