Inherited pericentric inversion (X)(p11.4q11.2) associated with delayed puberty and obesity in two brothers

We report two brothers with hypogonadotropic hypogonadism (HH), obesity and short stature associated with a maternally inherited pericentric inversion (X)(p11.4q11.2). On the basis that either breakpoint might disrupt a gene whose function is critical to normal sexual development we mapped the chromosomal breakpoints using two-colour fluorescent in situ hybridisation (FISH). The position of both the Xp11.4 and Xq11.2 breakpoints was refined using a panel of ordered BAC clones. No known genes were shown to map to the breakpoint regions. While we cannot entirely exclude the possibility that association between the clinical and cytogenetic phenotypes in the family is coincidental, it is possible that the inversion is responsible for HH through alternative molecular mechanisms such as position effects.     

inv(9)(p24q13) in three sterile brothers

Only nine non-polymorphic constitutional pericentric inversions of chromosome 9 have been described. We report on a familial inv(9)(p24q13) associated with sterility in three brothers. The mother's chromosomes were normal in blood lymphocytes (n=130); the father was already deceased and his karyotype unknown. However, the presence of any of the maternal chromosomes 9 (as assessed by C-banding) in her carrier children is inconsistent with the assumption of maternal mosaicism. Two single sisters were also carriers. The same rearranged chromosome 9 in the three sterile brothers can hardly be regarded as a fortuitous association, especially when the breakpoints are almost identical to those of the sole inversion previously found in an azoospermic male. If their father was a carrier, the observed sterility may be the result of 'chromosome anticipation', a phenomenon already invoked for certain familial chromosomal rearrangements.     

Brothers delay menarche and the onset of sexual activity in their sisters

The higher costs of sons compared with daughters extends to a negative effect of brothers on the lifetime reproductive success of their siblings in subsistence and preindustrial societies. In societies with fewer resource constraints, one might expect that these effects would be limited or non-existent. This study investigates the costs of brothers and sisters in a contemporary western society of adult Australians. Girls with elder brothers had a delayed age at menarche. Younger brothers were associated with delayed onset of sexual activity in sisters, but not in brothers. Neither younger nor elder brothers influenced fitness parameters (number of pregnancies, number of children, age at first pregnancy or age at first birth) in siblings of either sex. This study provides evidence that brothers negatively affect their sisters'' onset of reproductive maturity and sexual activity; however, this delay is not associated with a fitness cost in contemporary Australia. We suggest this is due to the long period of independence prior to child bearing.     

Fighting in fig wasps: do males avoid killing brothers or do they never meet them?

1. In many fig wasp species, armoured wingless males regularly engage in lethal fights for access to females inside figs, which act as discrete mating patches. 2. Kin selection generally opposes killing brothers, because their reproductive success provides indirect genetic benefits (inclusive fitness). However, siblicide may be avoided if (i) brothers do not occur in the same figs, or (ii) males avoid fighting brothers in the same fig. Alternatively, (iii) siblicide may occur because intense mate competition between brothers at the local scale overcomes kin selection effects, or (iv) males do not recognise kin. 3. A fig may also contain wasps from other closely related species and it is not known if males also fight with these individuals. 4. Nine microsatellite loci were used in the first genetic analysis of fighting in fig wasps. We assigned species and sibling identities to males and tested alternative fighting scenarios for three Sycoscapter wasp species in figs of Ficus rubiginosa. 5. Approximately 60% of figs contained males from more than one Sycoscapter species and approximately 80% of fights were between conspecifics, but a surprising 20% were between heterospecific males. 6. Within species, few figs contained brothers, suggesting that females typically lay one son per fig. Overall, most males do not compete with brothers and all fights observed were between unrelated males.     

Interaction of fraternal birth order and handedness in the development of male homosexuality

The present study investigated evidence for an interaction between two of the best established etiologic factors, or markers of etiologic factors, in the literature on male homosexuality: fraternal birth order and hand preference. By combining five samples, the authors produced study groups of 1774 right-handed heterosexuals, 287 non-right-handed heterosexuals, 928 right-handed homosexuals, and 157 non-right-handed homosexuals. The results showed a significant (P = 0.004) handedness by older brothers interaction, such that (a) the typical positive correlation between homosexuality and greater numbers of older brothers holds only for right-handed males, (b) among men with no older brothers, homosexuals are more likely to be non-right-handed than heterosexuals; among men with one or more older brothers, homosexuals are less likely to be non-right-handed than heterosexuals, and (c) the odds of homosexuality are higher for men who have a non-right hand preference or who have older brothers, relative to men with neither of these features, but the odds for men with both features are similar to the odds for men with neither. These findings have at least two possible explanations: (a) the etiologic factors associated with non-right-handedness and older brothers-hypothesized to be hyperandrogenization and anti-male antibodies, respectively-counteract each other, yielding the functional equivalent of typical masculinization, and (b) the number of non-right-handed homosexuals with older brothers is smaller than expected because the combination of the older brothers factor with the non-right-handedness factor is toxic enough to lower the probability that the affected fetus will survive.     

CFTR Haplotype Analysis Reveals Genetic Heterogeneity in the Etiology of Congenital Bilateral Aplasia of the Vas Deferens

Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in males with CBAVD revealed that in some males CBAVD is caused by two defective CFTR alleles. The genetic basis of CBAVD in the other males and its association with CF remained unclear. We undertook this study to test the hypothesis of commonality of CBAVD and CF by haplotype analysis, in the CFTR locus, of males suffering from CBAVD and of their families. According to the hypothesis of commonality of CBAVD and CF, two brothers with CBAVD are expected to carry the same two CFTR alleles, while their fertile brothers are expected to carry at least one different allele. Eleven families were studied, of which two families, with unidentified CFTR mutations, did not support this hypothesis. In these families two brothers with CBAVD inherited different CFTR alleles. Their fertile brothers inherited the same CFTR alleles as their brothers with CBAVD. These results provide evidence for genetic heterogeneity in CBAVD. Though in some families CBAVD is associated with two CFTR mutations, we suggest that in others it is caused by other mechanisms, such as mutations at other loci or homozygosity or heterozygosity for partially penetrant CFTR mutations.     

Case-control study of whether subfertility in men is familial.

OBJECTIVE--To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause. DESIGN--Case-control study and segregation analysis. SETTING--Two teaching hospitals in Leeds. SUBJECTS--Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department. MAIN OUTCOME MEASURES--The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers. RESULTS--Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families. CONCLUSION--Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.     

Quantitative and theoretical analyses of the relation between older brothers and homosexuality in men

Meta-analysis of aggregate data from 14 samples representing 10,143 male subjects shows that homosexuality in human males is predicted by higher numbers of older brothers, but not by higher numbers of older sisters, younger brothers, or younger sisters. The relation between number of older brothers and sexual orientation holds only for males. This phenomenon has therefore been called the fraternal birth order effect. Research on birth order, birth weight, and sexual orientation suggests that the developmental pathway to homosexuality initiated by older brothers operates during prenatal life. Calculations assuming a causal relation between older brothers and sexual orientation have estimated the proportion of homosexual men who owe their sexual orientation to fraternal birth order at 15% in one study and 29% in another. The maternal immune hypothesis proposes that the fraternal birth order effect reflects the progressive immunization of some mothers to male-specific antigens by each succeeding male fetus and the increasing effects of such immunization on sexual differentiation of the brain in each succeeding male fetus. There are at least three possible mechanisms by which the mother's immune response could influence the fetus: the transfer of anti-male antibodies across the placenta from the maternal into the fetal compartment, the transfer of maternal cytokines across the placenta, and maternal immune reactions affecting the placenta itself. This hypothesis is consistent with recent studies showing that the quantity of fetal cells that enter the maternal circulation is greater than previously thought, and that the number of male-specific proteins encoded by Y-chromosome genes is greater than previously thought.     

Sequence variation in the androgen receptor gene is not a common determinant of male sexual orientation.

To test the hypothesis that DNA sequence variation in the androgen receptor gene plays a causal role in the development of male sexual orientation, we have (1) measured the degree of concordance of androgen receptor alleles in 36 pairs of homosexual brothers, (2) compared the lengths of polyglutamine and polyglycine tracts in the amino-terminal domain of the androgen receptor in a sample of 197 homosexual males and 213 unselected subjects, and (3) screened the the entire androgen receptor coding region for sequence variation by PCR and denaturing gradient-gel electrophoresis (DGGE) and/or single-strand conformation polymorphism analysis in 20 homosexual males with homosexual or bisexual brothers and one homosexual male with no homosexual brothers, and screened the amino-terminal domain of the receptor for sequence variation in an additional 44 homosexual males, 37 of whom had one or more first- or second-degree male relatives who were either homosexual or bisexual. These analyses show that (1) homosexual brothers are as likely to be discordant as concordant for androgen receptor alleles; (2) there are no large-scale differences between the distributions of polyglycine or polyglutamine tract lengths in the homosexual and control groups; and (3) coding region sequence variation is not commonly found within the androgen receptor gene of homosexual men. The DGGE screen identified two rare amino acid substitutions, ser205-to-arg and glu793-to-asp, the biological significance of which is unknown.     

A normal male with an inherited deletion of one exon within the DMD gene

Summary We describe two brothers with identical inherited deletions of one single exon within the middle of the DMD gene; one brother has Becker muscular dystrophy diagnosed at 11 years of age, whereas the older brother is normal at 18. These results have implications for genetic counselling and prenatal diagnosis in families with Becker muscular dystrophy.     

Birth order and male androphilia in Samoan fa'afafine

The manner in which male androphilia is publicly expressed varies cross-culturally. As such, it is unclear whether distinct or common underlying causal processes characterize male androphilia in different cultures. Establishing the existence of cross-cultural universals in male androphilia is one means of ascertaining whether common biological bases underlie this phenomenon despite its culturally distinct forms. The evidence that the number of older biological brothers increases the odds of androphilia in later-born males has been well documented for Western samples (i.e. the fraternal birth order effect); but there is little evidence for this effect in non-Western samples. Here, we compare the birth order of androphilic males (i.e. fa'afafine) and gynephilic males from the politically autonomous Polynesian nation of Independent Samoa. Results indicate that relative to gynephilic males, fa'afafine tend to have more siblings and are generally later born when birth order is quantified using Slater, fraternal and sororal indices. More specifically, fa'afafine tend to have a greater number of older brothers, older sisters and younger brothers. We discuss the observed effects in relation to the differing reproductive patterns exhibited by the mothers of fa'afafine and gynephilic males, and to existing social and biological theories for sexual orientation.     

Relatedness among honeybees (Apis mellifera) of a drone congregation

The honeybee (Apis mellifera) queen mates during nuptial flights, in the so-called drone congregation area where many males from surrounding colonies gather. Using 20 highly polymorphic microsatellite loci, we studied a sample of 142 drones captured in a congregation close to Oberursel (Germany). A parentage test based on lod score showed that this sample contained one group of four brothers, six groups of three brothers, 20 groups of two brothers and 80 singletons. These values are very close to a Poisson distribution. Therefore, colonies were apparently equally represented in the drone congregation, and calculations showed that the congregation comprised males that originated from about 240 different colonies. This figure is surprisingly high. Considering the density of colonies around the congregation area and the average flight range of males, it suggests that most colonies within the recruitment perimeter delegated drones to the congregation with an equal probability, resulting in an almost perfect panmixis. Consequently, the relatedness between a queen and her mates, and hence the inbreeding coefficient of the progeny, should be minimized. The relatedness among the drones mated to the same queen is also very low, maximizing the genetic diversity among the different patrilines of a colony.     

Fraternal birth order and birth weight in probably prehomosexual feminine boys

The purpose of this study was to confirm a previous finding that homosexual males with older brothers weigh less at birth than do heterosexual males with older brothers. The subjects comprised 250 feminine boys referred to a child psychiatry service because of extreme cross-gender wishes or behavior and assumed, on the basis of previous research, to be prehomosexual, plus 739 control boys and 261 control girls referred to the same service for reasons unrelated to sexual orientation or gender identity disorder and assumed, from base-rate probabilities, to be preheterosexual. The feminine boys with two or more older brothers weighed 385 g less at birth than did the control boys with two or more older brothers (P = 0.005). In contrast, the feminine and control boys with fewer than two older brothers did not differ in birth weight. This finding suggests that the mechanism by which older brothers increase the odds of homosexuality in later-born males operates prior to the individual's birth. We hypothesize that this mechanism may be immunologic, that antimale antibodies produced by human mothers in response to immunization by male fetuses could decrease the birth weight of subsequent male fetuses as well as increase their odds of homosexuality.     

Large Inversion in Escherichia Coli K-12 1485in between Inversely Oriented Is3 Elements near Lac and Cdd

A companion study has shown that the inversion carried by strain 1485IN has one terminus between lac and proC and the other between his and cdd of the normal strain. Starting with this mapping data, we have done molecular work demonstrating that the inversion occurred by recombination between inversely oriented two IS3 elements, one present near lac and the other near the cdd locus; i.e., the inversion is IN(is3B-is3E). Evidence supporting this conclusion includes: (i) Normal and inversion strains share two short regions with identical restriction maps. One of these regions is near lac and the other near cdd. (ii) IS3 homology was detected in each of the terminus regions of both the normal and inversion strains. (iii) The sequence on one side of the original IS3 element near lac has been exchanged with the sequence on one side of the IS3 near cdd. Whether the inversion has occurred by one event of homologous recombination between the two IS3 elements or has been caused by involvement of IS3 elements on an F factor is discussed. Another rearrangement, probably related to inversion and deletion, was detected between the IS3 and cdd of the inversion strain.     

Supravalvular aortic stenosis. Autosomal dominant form of congenital cardiopathy

We describe a family in which two generations are affected: two brothers and one of their maternal uncles. One of their two half-sisters (same mother) is also suspected of having the same cardiopathy. This observation confirms the autosomal dominant transmission of the disease and shows its variable expressivity in the family under study.     

Heterogenous glycogen storage disease in one family.

Three brothers, aged 17, 14 and 4 ye presented. Deficiency of glucose-6-phosphatase was associated with deficiency of acid maltase in one and debranching enzyme in the other. Enzyme analyses could not be performed in the youngest sibling.     

Evaluation of the severity of hypoxanthine-guanine phosphoribosyltransferase deficiency using viable T cells

Peripheral T cells from 3 Lesch-Nyhan patients, 3 normal subjects, and 3 brothers with hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency but without Lesch-Nyhan syndrome (so-called partial deficiency) have been analyzed. Although these brothers contained HGPRT activities neither in the hemolysates nor in the T cell extracts at levels detectable by the regular radioenzyme assay, the enzyme deficiency had not caused any typical neurological symptoms of the Lesch-Nyhan syndrome. Although the T cells from these brothers were at least 10-fold more resistant to 6-thioguanine than normal T cells, they were more than 30-fold less resistant than the T cells from 3 Lesch-Nyhan patients indicating that there is a clear difference in the severity of the enzyme deficiency between the brothers and the Lesch-Nyhan patients. These data indicate that the long-term T cell culture in the medium containing a purine analog whose toxicity depends on a salvaging enzyme is useful for evaluating the severity of the enzyme deficiency in viable cells.     

Gender,family configuration,and the effect of family background on educational attainment

Abstract

A comprehensive model of family influences on educational resemblance of siblings expands the traditional sibling pair model to a full sibship model in order to investigate how gender, gender composition of sibships, and a measure of ordinal position moderate the effect of social origins on educational attainments of siblings. One common family factor is sufficient to explain the variation of educational attainment among brothers and sisters. Although effects of social origin variables on brothers are larger than on sisters, the relative effects of measured social origins are virtually the same among sisters and brothers. The disparity between educational attainments of brothers and sisters persists across sex composition and family size. Ordinal position does not alter the effects of social origins on educational attainment nor does it directly affect educational attainment. Father's and mother's education are equally important for all siblings regardless of birth order, gender composition, and family size.     

Incomplete trisomy 22

Summary Two brothers with duplication of the distal segment of 22q inherited from a t(6;22)(q27;13) translocation carrier mother presented with intraurine growth retardation, congenital hydrocephalus, cleft palate, genital hypoplasia with cryptorchidism and hypospadias, and similar facial features including mongoloid position of eyeaxes, hypertelorism, small nose with prominent bridge, prominent upper lip, and small mandible. In addition the second sib revealed renal hypoplasia, arrhinencephaly and pentalogy of Fallot. The patients died at ages eight days and one day, respectively. The two brothers appear to be the first instances of familial trisomy 22q13qter.