Concordance of iron indices in homozygote and heterozygote sibling pairs in hemochromatosis families: implications for family screening

Background/Aims: Concordance of iron indices between same sex siblings homozygous for the cysteine-to-tyrosine substitution at amino acid 282 (C282Y) mutation suggests that the variable phenotype in hereditary hemochromatosis is caused by genetic factors. Concordance of iron indices between same-sex heterozygous sibling pairs would provide further evidence of genetic modifiers of disease expression, and guidance for family screening strategies of subjects heterozygous for the C282Y mutation. Methods: We compared the iron indices of 35 C282Y homozygous and 35 C282Y heterozygous same-sex sibling pairs. To clarify whether concordance between siblings was due to environmental or genetic factors we compared the iron indices of 164 C282Y homozygous-normal, same-sex dizygotic twins. Results: Serum ferritin (r = 0.50, P = 0.003), hepatic iron concentration (r = 0.61, P = 0.025) and hepatic iron index (r = 0.67, P = 0.01) were highly concordant in C282Y homozygotes. Heterozygote siblings were concordant for serum ferritin (r = 0.76, P = 0.0001) and transferrin saturation (r = 0.79, P = 0.0001). Homozygote-normal same-sex dizygotic twins were concordant for serum ferritin (r = 0.62, P = 0.0001) but not for transferrin saturation. Conclusions: Concordance of iron indices exists in C282Y homozygote and heterozygote sibling pairs. Siblings of expressing C282Y heterozygotes require phenotypic assessment. These data provide evidence for modifying genes influencing disease expression in hemochromatosis. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

Replicated linkage for eye color on 15q using comparative ratings of sibling pairs

The aim of the study was to perform a genetic linkage analysis for eye color, for comparative data. Similarity in eye color of mono- and dizygotic twins was rated by the twins' mother, their father and/or the twins themselves. For 4748 twin pairs the similarity in eye color was available on a three point scale (not at all alike-somewhat alike-completely alike), absolute eye color on individuals was not assessed. The probability that twins were alike for eye color was calculated as a weighted average of the different responses of all respondents on several different time points. The mean probability of being alike for eye color was 0.98 for MZ twins (2167 pairs), whereas the mean probability for DZ twins was 0.46 (2537 pairs), suggesting very high heritability for eye color. For 294 DZ twin pairs genome-wide marker data were available. The probability of being alike for eye color was regressed on the average amount of IBD sharing. We found a peak LOD-score of 2.9 at chromosome 15q, overlapping with the region recently implicated for absolute ratings of eye color in Australian twins [Zhu, G., Evans, D. M., Duffy, D. L., Montgomery, G. W., Medland, S. E., Gillespie, N. A., Ewen, K. R., Jewell, M., Liew, Y. W., Hayward, N. K., Sturm, R. A., Trent, J. M., and Martin, N. G. (2004). Twin Res. 7:197-210] and containing the OCA2 gene, which is the major candidate gene for eye color [Sturm, R. A. Teasdale, R. D, and Box, N. F. (2001). Gene 277:49-62]. Our results demonstrate that comparative measures on relatives can be used in genetic linkage analysis.

Sex Differences in Symptoms of Depression in Unrelated Individuals and Opposite-Sex Twin and Sibling Pairs

Diagnosis of a major depressive episode by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association requires 5 out of 9 symptoms to be present. Therefore, individuals may differ in the specific symptoms they experience and reach a diagnosis of depression via different pathways. It has been suggested that depressed women more often report symptoms of sleep disturbance, appetite or weight disturbance, fatigue, feelings of guilt/worthlessness and psychomotor retardation than depressed men. In the current study, we investigate whether depressed men and women differ in the symptoms they report. Two samples were selected from a sample of Dutch and Australian twins and siblings. First, Dutch and Australian unrelated depressed individuals were selected. Second, a matched epidemiological sample was created consisting of opposite-sex twin and sibling pairs in which both members were depressed. No sex differences in prevalence rates for symptoms were found, with the exception of decreased weight in women in the sample of unrelated individuals. In general, the similarities in symptoms seem to far outweigh the differences in symptoms between men and women. This signifies that men and women are alike in their symptom profiles for major depression and genes for depression are probably expressed in the same way in the two sexes.

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R-avg) and then weighted for sample size (rootN[affected cases]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P-AvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P-ord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (P-AvgRnk

The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients

Type 1 diabetes (T1D) is a multifactorial autoimmune disease, with strong genetic component. Several susceptibility loci contribute to genetic predisposition to T1D. One of these loci have been mapped to chromosome 1q42 in UK and US joined affected family data sets but needs to be replicated in other populations. In this study, we evaluated sixteen microsatellites located on 1q42 for linkage with T1D in 97 Russian affected sibling pairs. A 2.7-cm region of suggestive linkage to T1D between markers D1S1644 and D1S225 was found by multipoint linkage analysis. The peak of linkage was shown for D1S2847 (P = 0.0005). Transmission disequilibrium test showed significant undertransmission of the 156-bp allele of D1S2847 from parents to diabetic children (28 transmissions vs. 68 nontransmissions, P = 0.043) in Russian affected families. A preferential transmission from parents to diabetic offspring was also shown for the T(-25) and T1362 alleles of the C/T(-25) and C/T1362 dimorphisms, both located at the TAF5L gene, which is situated 103 kb from D1S2847. Together with the A/C744 TAF5L SNP, these markers share common T(-25)/A744/T1362 and C(-25)/C744/T1362 haplotypes associated with higher and lower risk of diabetes (Odds Ratio = 2.15 and 0.62, respectively). Our results suggest that the TAF5L gene, encoding TAF5L-like RNA polymerase II p300/CBP associated factor (PCAF)-associated factor, could represent the susceptibility gene for T1D on chromosome 1q42 in Russian affected patients.

Genomewide Linkage Scan of 409 European-ancestry and African American Families with Schizophrenia: Suggestive Evidence of Linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the Combined Sample

We report the clinical characteristics of a schizophrenia sample of 409 pedigrees-263 of European ancestry ( EA) and 146 of African American ancestry ( AA)-together with the results of a genome scan ( with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia ( SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs ( ASPs) ( 279 EA and 124 AA) and 100 all-possible half-sibling ASPs ( 15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 ( empirical Z likelihood-ratio score [ Z(lr)] threshold >= 2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z(lr) scores >= 2.0 in 8p were observed from 30.7 cM to 61.7 cM ( Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z(lr) of 3.25 ( equivalent Kong-Cox LOD of 2.30) near D8S1771 ( at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 ( NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families.

HLA and Genomewide Allele Sharing in Dizygotic Twins

Gametic selection during fertilization or the effects of specific genotypes on the viability of embryos may cause a skewed transmission of chromosomes to surviving offspring. A recent analysis of transmission distortion in humans reported significant excess sharing among full siblings. Dizygotic (DZ) twin pairs are a special case of the simultaneous survival of two genotypes, and there have been reports of DZ pairs with excess allele sharing around the HLA locus, a candidate locus for embryo survival. We performed an allele-sharing study of 1,592 DZ twin pairs from two independent Australian cohorts, of which 1,561 pairs were informative for linkage on chromosome 6. We also analyzed allele sharing in 336 DZ twin pairs from The Netherlands. We found no evidence of excess allele sharing, either at the HLA locus or in the rest of the genome. In contrast, we found evidence of a small but significant (P = .003 for the Australian sample) genomewide deficit in the proportion of two alleles shared identical by descent among DZ twin pairs. We reconciled conflicting evidence in the literature for excess genomewide allele sharing by performing a simulation study that shows how undetected genotyping errors can lead to an apparent deficit or excess of allele sharing among sibling pairs, dependent on whether parental genotypes are known. Our results imply that gene-mapping studies based on affected sibling pairs that include DZ pairs will not suffer from false-positive results due to loci involved in embryo survival.

Searching behaviour and diet of Oystercatcher Haematopus ostralegus pairs feeding in their territories

Search path, searching behaviour and diet of pairs of Oystercatchers feeding in mudflat territories were studied during spring. females ate Nereis, Mya, small unidentified prey, probably Corophium, and a few Macoma, whereas males primarily ate Macoma. Even when female and male foraged in the same site, they often caught different prey. The combination of 'The Search-rate/Detection Model' (Gendron & Staddon 1983) and 'The Harvestable Prey Model' (Zwarts & Wanink 1993) provide the theoretical framework in which to explain these differences in diet. Macoma are thought to be more cryptic than Nereis, Mya and Corophium. Therefore females, while searching at a faster rate than their respective mates, caught far fewer cryptic prey, but a greater number of more conspicuous prey than their mates. On the basis of distances moved before and after capturing prey, males exhibited area-restricted searching for Macoma and Corophium. In contrast, females did not exhibit any area-restricted searching. it is suggested that the distribution of Macoma and Corophium available to males searching slowly was more clumped than that of these two prey species available to females searching more quickly.

Sibling competition and parental control: Patterns of begging in parrots

Begging and food allocation patterns are the outcome of complex and repeated interactions between parents and young. In most systems studied, food allocation is regulated by begging and scramble competition. In contrast, little is understood about how nestling solicitation behaviours will evolve in systems where parents engage in complex patterns of food allocation. Parrots appear to be an excellent group in which to examine the shifting balance between sibling competition and parental control. Studies to date have shown that levels of sibling competition within parrot broods are low, possibly in response to parental control over food distribution. I assess what is known about the function of nestling begging in parrots and evaluate why begging signals appear to function differently in this group.

A comparison of family functioning, temperament, and childhood conditions in monozygotic twin pairs discordant for lifetime bulimia nervosa

Objective: The authors investigated differences between twins in nine pairs of female monozygotic twins in the Australian Twin Registry who were discordant for lifetime bulimia nervosa. Method: The twins affected and unaffected by lifetime bulimia nervosa were compared on self-report measures, including a measure of parental bonding, four measures of temperament, and six early-childhood medical conditions. Results: No twins had current bulimia nervosa, and there was no difference in weight or eating status between the affected and unaffected twins. The affected twins reported significantly lower self-esteem and less warmth but more overprotection by their mothers during childhood. Conclusions: Although limited by the small number of discordant twin pairs and the inability to detect causal relationships, these results suggest that environmental influences that promote low self-esteem may also increase the risk for bulimia nervosa. These temperamental differences may explain the discrepancies in parenting or perceived parenting.

Mating behaviour and alternative oviposition sites for male eggs in the heteronomous hyperparasitoid Coccophagus gurneyi Compere (Hymenoptera : Aphelinidae)

The aphelinid parasitoid Coccophagus gurneyi Compere has unusual sex-related host relationships. Females are diploid and develop internally within mealybugs Pseudococcus calceolariae (Maskell). Males, in contrast, are haploid and hyperparasitic, developing on primary parasitoid larvae within the mealybugs. Furthermore, males have been claimed to be capable of either internal or external development, depending on the precise site of deposition of the haploid egg. This diversity of developmental pathways could indicate the existence of a sibling-species complex. We therefore quantified the mating and ovipositional behaviour of C. gurneyi, for comparison with that of an undescribed sibling species. We also checked whether the females deposit male eggs in alternative sites. The pattern of mating was found to be typical of mating behaviour in Coccophagus spp. and was consistent among all mating pairs, suggesting that the colony comprised one species. Further, the mating behaviour was significantly different from that of the undescribed sibling species. The site of male egg deposition varied and is apparently dictated by two factors; whether the mealybug is parasitised and, if so, the size of the parasitoid it contains. If the mealybugs were unparasitised or if the parasitoids within the mealybugs were small (< 0.53 mm), male eggs were deposited within the mealybug haemocoel. If the parasitoids were large (> 1.05 mm), male eggs were deposited within the parasitoids. These results support the claim of alternate host relationships and developmental pathways within males of C. gurneyi.

Descriptions of the Anopheles (Cellia) farauti complex of sibling species (Diptera : Culicidae) in Australia

Descriptions of the three sibling species of the Anopheles farauti complex in Australia, A. farauti Laveran (formerly A. farauti No. 1), A. hinesorum Schmidt sp.n. (formerly A. farauti No. 2) and A. torresiensis Schmidt sp.n. (formerly A. farauti No. 3) are provided. These species form a part of the punctulatus group, which contains the major malaria vectors in the southwest Pacific. Morphological markers are described for adult females, fourth instar larvae and pupae which identify most specimens, and are presented in keys.