Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins.

Mice homozygous for the recessive mutation motheaten (me) are deficient in capacity for immune response but show an elevated level of serum immunoglobulins. In comparison to spleen cells from normal sibs, spleen cells from me/me mice have a severely depressed 19S PFC response to SRBC. In the GVH assay, spleen and thymus cells from motheaten donors caused significantly weaker reactions than like cells from normal sibs. Serum electrophoretic patterns of motheaten mice showed increased levels of alpha-, beta-, and gamma-globulins and decreased levels of albumin. Increases in quantities of all major classes of immunoglobulins were found in serum of me/me mice 5 weeks of age and older. Elevation of serum IgM was evident by 3 weeks of age and had reached 25 times the levels in normal sibs by 6 weeks of age. Immunoelectrophoresis and Ouchterlony analysis showed motheaten serum to have both kappa and lambda2 light chains. Evidence of autoimmunity was found in motheaten mice in the granular deposition of IgM and IgG in kidney glomeruli. Motheaten mice, thus, appear to have a severe immune deficiency, but the basic nature of the deficiency is not yet known.     

Neuropsychological Characteristics of Cortical and Subcortical Zones of the Human Brain as Multidimensional Genetic Risk Factors of Schizophrenia

A neuropsychological study of 59 families with schizophrenia (193 subjects: 59 patients, 109 parents, and 25 sibs) was conducted using the methods of A.R. Luria. The control group included 23 healthy subjects without a familial history of schizophrenia. The analysis revealed a wide spectrum of mental disorders in schizophrenics and their relatives but not in the control group. The disorders varied from vague to distinct. The most informative for discrimination of the subject groups were interrelated integrative characteristics of the left and right subcortical, left subcortico-frontal, and left subcortico-temporal areas. The errors of discrimination between schizophrenics and control subjects (a low-risk group) and between the low-risk group and sibs (a high-risk group) ranged from 7 to 19%. The multidimensional neuropsychological indicators revealed may be used for further analysis of genetic risks of schizophrenia.     

Strategies for implementing genomic selection in family-based aquaculture breeding schemes: double haploid sib test populations

Background

Simulation studies have shown that accuracy and genetic gain are increased in genomic selection schemes compared to traditional aquaculture sib-based schemes. In genomic selection, accuracy of selection can be maximized by increasing the precision of the estimation of SNP effects and by maximizing the relationships between test sibs and candidate sibs. Another means of increasing the accuracy of the estimation of SNP effects is to create individuals in the test population with extreme genotypes. The latter approach was studied here with creation of double haploids and use of non-random mating designs.

Methods

Six alternative breeding schemes were simulated in which the design of the test population was varied: test sibs inherited maternal (Mat), paternal (Pat) or a mixture of maternal and paternal (MatPat) double haploid genomes or test sibs were obtained by maximum coancestry mating (MaxC), minimum coancestry mating (MinC), or random (RAND) mating. Three thousand test sibs and 3000 candidate sibs were genotyped. The test sibs were recorded for a trait that could not be measured on the candidates and were used to estimate SNP effects. Selection was done by truncation on genome-wide estimated breeding values and 100 individuals were selected as parents each generation, equally divided between both sexes.

Results

Results showed a 7 to 19% increase in selection accuracy and a 6 to 22% increase in genetic gain in the MatPat scheme compared to the RAND scheme. These increases were greater with lower heritabilities. Among all other scenarios, i.e. Mat, Pat, MaxC, and MinC, no substantial differences in selection accuracy and genetic gain were observed.

Conclusions

In conclusion, a test population designed with a mixture of paternal and maternal double haploids, i.e. the MatPat scheme, increases substantially the accuracy of selection and genetic gain. This will be particularly interesting for traits that cannot be recorded on the selection candidates and require the use of sib tests, such as disease resistance and meat quality.     

Long term follow-up of two sibs with an autosomal recessive form of chrondrodysplasia punctata and epilepsy

Long term follow-up of two sibs with an autosomal recessive form of chrondrodysplasia punctata and epilepsy: A variety of osteodysplasias are referred to with the term chondrodysplasia punctata (CDP). Here we report on two sibs, a boy and a girl, with probable autosomal recessive form of CDP and epilepsy followed-up for 30 and 19 years, respectively. Family history was unremarkable but for consanguinity. Pregnancies and deliveries were uneventful. At birth, length was 46 (-3SD) and 45 (-4SD) cm, respectively. Craniofacial dysmorphism was noted: severe nasal hypoplasia, flat face, hypertelorism, a low nasal bridge, short stature. Skeletal abnormalities included epiphyseal stippling in the thoracic spine, bilateral proximal and distal humeri, femur, tibia and bilateral carpal and tarsal bones. The boy had a hemivertebrae T12, with absence of a rib. After the age of 6 years facial dysmorphism had improved. Final height was 154 cm (-3SD) in the boy and 158 cm (-0,5SD) in the girl. The boy was operated on for scoliosis. Both sibs had club feet, the girl had also genu valgum. IQ was evaluated to be 55 in the girl and 83 in the boy. The first non febrile generalized seizure appeared in the boy when he was 11 months of age, and in the girl when she was 25 months of age. Both had many other seizures and were taking antiepileptics. EEG were abnormal. Karyotypes were normal. Extensive screening for metabolic disorders was normal. Acquired in utero CDP were excluded. We suggest the sibs described in this report have yet another provisionally unique possibly autosomal recessive syndrome, with CDP and epilepsy as phenotypic traits.     

A major histocompatibility complex in the toadxenopus laevis (Daudin)

The genetic relationship between mixed leukocyte reaction (MLR), skin graft rejection, and some red blood cell antigens has been studied in a sibship of the toadXenopus laevis. MLR typing was achieved using blood lymphocytes. The graft experiments were performed at 17–19°C. Grafts exchanged between MLR identical sibs were rejected in 30.9±5.1 days, grafts exchanged between MLR different sibs were rejected in 20.4±2.4 days when animals differed at one MLR haplotype, and in 18.6±1.9 days when they differed at two MLR haplotypes. Immunizations and absorptions following the MLR typing produced agglutinating antisera that recognize red blood cell antigens segregating with MLR haplotypes. The results parallel those obtained in various mammalian and avian species and suggest that the homology of the major histocompatibility complex (MHC), described in higher vertebrates, can be extended to amphibians.     

Familial hemiplegic migraine locus on 19p13 is involved in the common forms of migraine with and without aura

Migraine is a common neurological disease of two main types: migraine with aura and migraine without aura. Familial clustering suggests that genetic factors are involved in the etiology of migraine. Recently, a gene for familial hemiplegic migraine, a rare autosomal dominant subtype of migraine with aura, was mapped to chromosome 19p13. We tested the involvement of this chromosomal region in 28 unrelated families with the common forms of migraine with and without aura, by following the transmission of the highly informative marker D19S394. Sibpair analysis showed that affected sibs shared the same marker allele more frequently than expected by chance. Our findings thus also suggest the involvement of a gene on 19p13 in the etiology of the common forms of migraine.     

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.     

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 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.     

HLA haplotype segregation in families of type 1 diabetics

The hypothesis of linkage between HLA and a disease susceptibility (DS) locus (or loci) for type 1 diabetes was tested. HLA segregation was random among 57 non-diabetic sibs but not among 39 diabetic sibs, suggesting that susceptibility to type 1 diabetes may be due to an HLA-linked gene(s). The data did not fit a genetic model involving either a single recessive or dominant gene. The excess of HLA-identical diabetic sibs and the reduced number who were HLA-discordant compared to expected numbers indicated that factors from both paternal and maternal haplotypes were necessary for DS. In 1 of the 3 families with a diabetic parent and more than one diabetic sib, the diabetic sibs inherited different haplotypes from the affected parent, suggesting that either of these haplotypes conferred DS. HLAB 8, B 18 and B 40 were increased in frequency among 97 unrelated type 1 diabetics compared with 238 controls, especially among those with onset age less than 10 years. This early onset group may represent a subtype of type 1 diabetes.     

Discrimination of family‐specific odours by juvenile coho salmon: roles of learning and odour concentration*

Free‐swimming coho salmon fry Oncorhynchus kisutch of some families showed preference (relative to the behaviour of naïve sibs) for the odours of similarly aged non‐sibs to whom they had been exposed during the post‐hatch (alevin) stage and the early free‐swimming (fry) stage, but not the embryo (egg) stage, indicating that odour‐learning had occurred during the later developmental periods. Recognition (i.e. preference) of sib‐ pecific odours was evident after a month, and in one case 5 months, of separation from those odours. Thus, young salmon incubating in their gravel nests in streams appear to have the capacity to learn the chemical characteristics of conspecifics and retain this memory for at least several months without reinforcement. However, in addition to the general attractiveness of sibs and familiar non‐sibs over unfamiliar non‐sibs, some non‐sibs were consistently more attractive than others. Preference between two different non‐sib odours could be reversed by changing their relative concentrations, indicating that relative attractiveness is a function of both familiarity and odour concentration. Therefore, although juvenile coho salmon learn, remember, and are subsequently attracted by sib‐specific odours in early life, familiar odours are not always preferred over unfamiliar conspecific odours. Preference in dyadic assays is therefore an insensitive measure of recognition.     

Oligodactyly and multiple synostoses of the extremities: Two cases in sibs

Summary Two sibs with a rare phenotype of oligodactyly with metacarpal, carpal, radioulnar, and metatarsal synostoses and shortening of the forearms were born of healthy parents. Genetic counselling with regard to future children of one of these sibs was given on the assumption of an autosomal recessive inheritance, which is highly probable, judging from the other rare familial cases found in the literature.     

Inclusion of unaffected sibs increases power in model-free linkage analysis of a behavioral trait

Study design strategies are of critical importance in the search for genes underlying complex diseases. Two important design choices in planning gene mapping studies are the analytic strategy to be used, which will have an impact on the type of data to be collected, and the choice of genetic markers. In the present paper, we used the simulated behavioral trait data provided in the Genetic Analysis Workshop 14 to: 1) investigate the usefulness of incorporating unaffected sibs in model-free linkage analysis and, 2) compare linkage results of genome scans using a 7-cM microsatellite map with a 3-cM single nucleotide polymorphisms map. To achieve these aims, we used the maximum-likelihood-binomial method with two different coding approaches. We defined the unaffected sibs as those totally free of phenotypes correlated to the disease. Without prior knowledge of the answers, we were able to correctly localize 2 out of 5 loci (LOD > 3) in a sample of 200 families that included the unaffected sibs but only one locus when based on an affected-only strategy, using either microsatellite or SNPs genome scan. LOD scores were considerably higher using the analytic strategy which incorporated the unaffected sibs. In conclusion, including unaffected sibs in model-free linkage analysis of complex binary traits is helpful, at least when complete parental data are available, whereas there are no striking advantages in using single nucleotide polymorphisms over microsatellite map at marker densities used in the current study.     

Familial study of vesico-ureteral reflux

We report our results of a retrospective study of vesico-ureteral reflux based on the families of 66 index patients. The recurrence risk for sibs is 9,3%. With a prospective approach (ultrasound and uroradiology), the proportion of affected sibs is 26,6%. Our results are discussed with reference to the data of the literature.