A prezygotic transmission distorter acting equally in female and male zebra finches Taeniopygia guttata

The two parental alleles at a specific locus are usually inherited with equal probability to the offspring. However, at least three processes can lead to an apparent departure from fair segregation: early viability selection, biased gene conversion and various kinds of segregation distortion. Here, we conduct a genome‐wide scan for transmission distortion in a captive population of zebra finches (Taeniopygia guttata) using 1302 single‐nucleotide polymorphisms (SNPs) followed by confirmatory analyses on independent samples from the same population. In the initial genome‐wide scan, we found significant distortion at three linked loci on chromosome Tgu2 and we were able to replicate this finding in each of two follow‐up data sets [overall transmission ratio = 0.567 (95% CI = 0.536–0.600), based on 1101 informative meioses]. Although the driving allele was preferentially transmitted by both heterozygous females [ratio = 0.560 (95% CI = 0.519–0.603)] and heterozygous males [ratio = 0.575 (95% CI = 0.531–0.623)], we could rule out postzygotic viability selection and biased gene conversion as possible mechanisms. Early postzygotic viability selection is unlikely, because it would result in eggs with no visible embryo and hence no opportunity for genotyping, and we confirmed that both females and males heterozygous for the driving allele did not produce a larger proportion of such eggs than homozygous birds. Biased gene conversion is expected to be rather localized, while we could trace transmission distortion in haplotypes of several megabases in a recombination desert. Thus, we here report the rare case of a prezygotically active transmission distorter operating equally effectively in female and male meioses.     

Meiotic disjunction and embryonic lethality in trisomies derived from an X-linked translocation in the onion fly,Hylemya antiqua (Meigen)

Translocation- and tertiary trisomies (for the X-chromosomes) were obtained after testcrossing translocation heterozygous females of an X-linked “simple” translocation stock. Meiotic disjunction as judged from segregations at M II (males) and in young eggs of testcrosses (males and females) in translocation trisomics was studied. No progeny of tertiary trisomic males and females was found, but male M II could be studied. Six different orientation types appeared in translocation trisomie (2n + 1) males and these were present in equal frequencies. No adjacent II configurations were found. The small X- and Y-chromosomes and the large translocated X-chromosome of the translocation complex disjoin at random (n and n + 1 gametes) in both translocation- and tertiary trisomic males. In translocation trisomic females four different orientation types appeared. From the high frequency of two of these (together, 94.5%) it is concluded that the two normal X-chromosomes show preferential pairing and disjunction, while the translocated X-chromosome moves to either one of the two poles at random. Primary trisomic (for the X-chromosome) males (XXY) and females (XXX) were obtained from testerossed translocation trisomics. Cytological analysis of adult male progeny of testerossed XXY males showed that no random orientation for the X-, X- and Y-chromosomes occurred because half of the sons was disomic (XY) and half of them trisomic (XXY). A possible mechanism is discussed. Analysis of young eggs of testerossed XXX females indicated a segregation of 2X∶1X=1∶1. The level of “semi”-sterility as scored from testcrosses of translocation trisomies appeared to be as in translocation heterozygotes. Here again a close relation exists between “semi”-sterility and deficiencies in eggs for a large chromosomal segment. The possible use of this translocation for genetic control of insect pests is discussed.     

Nonsyndromic cleft lip with or without cleft palate in west Bengal, India: evidence for an autosomal major locus.

Ninety extended families having one or more individuals affected with nonsyndromic cleft lip (CL) with or without cleft palate (CL/P) were ascertained in rural West Bengal, India. These families included 138 affected people, 64% of whom had CL alone and 66% of whom were male. Multiple-affected-member ("multiplex") pedigrees were less common than single-affected-member ("simplex") pedigrees, composing 34% of all extended pedigrees. There was no difference between multiplex and simplex pedigrees in the frequency of affected persons with CL alone, but multiplex pedigrees had a lower frequency of affected males (58%) than did simplex pedigrees (76%; P = .02). Complex segregation analysis using the POINTER computer program rejected both the hypothesis of no familial transmission (P < .0001) and the hypothesis that familiarity could be explained solely by a multifactorial/threshold model (P < .05). The hypothesis of major-locus inheritance alone could not be rejected. Among major-locus models examined, strictly recessive inheritance was rejected (P < .0001), but codominant and dominant models were not. Neither the addition of a multifactorial component nor the addition of a proportion of sporadic cases to the major-locus model improved the fit of the data. In conclusion, the results of complex segregation analysis were consistent with a dominant or codominant major-locus mode of inheritance of CL/P in these families.     

Male inbreeding status affects female fitness in a seed-feeding beetle

Inbreeding generally reduces male mating activity such that inbred males are less successful in male-male competition. Inbred males can also have smaller accessory glands, transfer less sperm and produce sperm that are less motile, less viable or have a greater frequency of abnormalities, all of which can reduce the fertilization success and fitness of inbred males relative to outbred males. However, few studies have examined how male inbreeding status affects the fitness of females with whom they mate. In this study, we examine the effect of male inbreeding status (inbreeding coefficient f = 0.25 vs. f = 0) on the fecundity, adult longevity and the fate of eggs produced by outbred females in the seed-feeding beetle, Callosobruchus maculatus. Females mated to inbred males were less likely to lay eggs. Of those that laid eggs, females mated to inbred males laid 6-12% fewer eggs. Females mated to inbred males lived on average 5.4% longer than did females mated to outbred males, but this effect disappeared when lifetime fecundity was used as a covariate in the analysis. There was no effect of male inbreeding status on the proportion of a female's eggs that developed or hatched, and no evidence that inbred males produced smaller nuptial gifts. However, ejaculates of inbred males contained 17-33% fewer sperm, on average, than did ejaculates of outbred males. Our study demonstrates that mating with inbred males has significant direct consequences for the fitness of female C. maculatus, likely mediated by effects of inbreeding status on the number of sperm in male ejaculates. Direct effects of male inbreeding status on female fitness should be more widely considered in theoretical models and empirical studies of mate choice.     

Estimation of male to female ratio of mutation rates from carrier-detection tests in X-linked disorders.

A method is presented for the estimation of the ratio of male to female mutation rates from female carrier-detection test data from pedigrees containing an isolated male manifesting an X-linked necessive disorder. Pedigrees of any size and complexity (barring consanguinity) and containing any number of tested females can be utilized. The relative fitness of affected males and carrier females, and the segregation probability of the abnormal gamete in females, can be estimated simultaneously with the ratio of mutation rates in order to test specific hypotheses against given bodies of data. Here this method is applied to families containing isolated individuals affected with Lesch-Nyhan syndrome.     

Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation.

Eighty-nine index patients from 85 families were defined as having Leber hereditary optic neuropathy (LHON) by the presence of one of the mtDNA mutations at positions 11778 (66 families), 3460 (8 families), or 14484 (11 families). There were 62 secondary cases. Overall, 64% of index cases had a history of similarly affected relatives. The ratios of affected males to affected females were 3.7:1 (11778), 4.3:1 (3460), and 7.7:1 (14484). The 95th centile for age at onset of symptoms was close to 50 years in index, secondary, male, and female patients. There were no differences in the distributions of age at onset between different mutation groups, between index and secondary cases, or between males and females, apart from this being slightly later in all female patients than in male 11778 patients. There was no significant correlation between age at onset in index cases and that in their affected siblings or cousins. Heteroplasmy (< 96% mutant mtDNA) was detected in 4% of affected subjects (67%-90% mutant mtDNA) and in 13.6% of 140 unaffected relatives (< 5%-90% mutant mtDNA). Analysis of all pedigrees, excluding sibships < 50 years of age and index cases, indicated recurrence risks of 30%, 8%, 46%, 10%, 31%, and 6%, respectively, to the brothers, sisters, nephews, nieces, and male and female matrilineal first cousins of index cases. Affected females were more likely to have affected children, particularly daughters, than were unaffected female carriers. The pedigree data were entirely compatible with the previously proposed X-linked susceptibility locus, with a gene frequency of .08, penetrance of .11 in heterozygous females, and 40% of affected females being homozygous, the remainder being explained by heterozygosity and disadvantageous X inactivation.     

Meiotic disjunction,sex-determination and embryonic lethality in an X-linked “Simple” translocation of the onion fly,Hylemya antiqua (Meigen)

It was shown that the translocation in study is X-linked. After testcrossing translocation heterozygous males they generally only produce translocation heterozygous daughters and normal sons. The small acrocentric chromosomes involved in the translocation appeared to be the sex-chromosomes. The X-chromosome has a secondary constriction which is missing in the (male determining) Y-chromosome. Meiotic orientation was studied in translocation heterozygous males and females. The alternate and adjacent I orientations were found in about equal frequencies. Further, numerical meiotic non-disjunction (two types) occurred in translocation heterozygous males (about 2%), but is much higher in females (18.7%). In (achiasmate) males the homologous centromeres predominantly regulate meiotic pairing, coorientation and disjunction, apparently independently of the chromosomal rearrangement. Disturbed telomere pairing in particular leading to reduced chiasma frequency most probably explains the high numerical non-disjunction in chiasmate females. A rather good relationship exists between the percentage “semi”-sterility (28%), scored as late embryonic lethals (eggs, 72 hrs.) and the percentage karyotypes (20%) in young eggs (8–16 hrs.) with a large chromosomal deficiency. The remaining sterility (8%) can be explained by the somewhat decreased viability of tertiary trisomics and duplication karyotypes at the end of the egg stage. This translocation behaves like a “simple” one.     

RFLP analysis in families with sporadic hemophilia A

Summary To investigate the sporadic occurrence of hemophilia A and to estimate the sex ratio of mutation rates directly, 17 families with isolated cases of the disorder were studied by RFLP analysis and by clotting assays. Three RFLPs, one intragenic and two with close linkage to hemophilia A, were used. In eight families the RFLP study excluded the carrier status of the maternal grandmothers. Since hemostatic studies showed that the eight mothers of these propositi were hemophilia carriers, the origin of the newly mutated genes was inferred from the RFLP patterns: six hemophilic genes derived from the normal maternal grandfathers and two, from maternal grandmothers. The data indicate a higher mutation rate in males than in females, as previously suggested by segregation analysis and coagulation studies. However the sex ratio indicated by the RFLP analysis is lower than previously reported and could explain previous conflicting estimates.     

Segregation of genetic hemochromatosis indexed by latent capacity of transferrin.

A genetic analysis of the segregation of hereditary hemochromatosis, indexed by the measurement of latent capacity of transferrin (LCAP), was undertaken in an ascertained sample of 147 pedigrees from Brittany, France. There were no mean differences by sex in the distribution of LCAP in the control sample, although in the family data there was a higher representation of males with low values than of females with low values, consistent with the higher proportion of affected males. The results of bivariate segregation analysis revealed no systematic evidence for heterozygous expression either in the biochemical domain of LCAP abnormalities or in increased liability to overt symptomatic disease. Joint consideration of the quantitative variable with hemochromatosis affection status allowed clear resolution of a recessive single-gene inheritance pattern in these families.     

Cultural inheritance of the desire for male offspring and the incidence of a sex‐linked lethal disease

Abstract

This paper studies the effect of having at least one male offspring on a sex‐linked recessive disease and the fraction of affected males due to fresh mutations. The equilibrium frequency of heterozygous females depends not only on the intensity of the reproductive compensation, but also on the time of mutational change. It has been shown that the frequency ranges from 4u without reproductive compensation to √2u or √3u with strict compensation, where u is the mutation rate from the wild type allele to lethal gene. The frequency √2u is achieved when mutation occurs in mature germ cells, whereas, √3u achieved when mutation occurs in early development of germ cells. This increased frequency of heterozygous females due to reproductive compensation reduces considerably the proportion of affected males due to fresh mutation.     

Biochemical evidence of haplodiploidy in the whiteflyBemisia tabaci

Polymorphic esterase and acetylcholinesterase alleles in the whiteflyBemisia tabaci were studied using electrophoretic and colorimetric assays. The segregation of these alleles between parental and F₁ generations provided unequivocal evidence of haplodiploidy in this pest species. Unmated females, heterozygous at a polymorphic locus, produced a 1:1 ratio of haploid males expressing either of the maternal alleles. Although male offspring were produced by both virgin and mated females, the segregation of alleles showed they were always haploid (hemizygous) for the marker enzymes. Females only arose from fertilized eggs and invariably expressed paternal and maternal alleles.     

Paternity analysis in the golden egg bug using AFLPs: do the males preferentially accept their true genetic offspring?

Abstract.  1. The evolution of parental care and intraspecific parasitism involve conflicts of interest between mothers and other potential care givers who contribute to enhance offspring survival. In the golden egg bug, Phyllomorpha laciniata Villers (Heteroptera: Coreidae), females lay eggs on conspecifics and on plants. The adaptive significance of egg carrying in this species has been the subject of some controversy, which can only be resolved by determining the genetic relationship between the eggs and the adult who carries them. This study examined whether male acceptance of true genetic offspring occurs with a higher frequency than that expected from random oviposition on conspecifics.
2. Paternity analysis, using Amplified Fragment Length Polymorphism (AFLP) markers, was conducted on eggs carried by males housed with field-mated females.
3. Out of the total number of eggs sired by males in the experimental groups, the proportion of eggs carried by males that were their true genetic offspring was 30.8%.
4. Monte Carlo methods show that the probability of a male accepting an egg that is his true genetic offspring is higher than expected if females dumped eggs on males at random.
5. These results suggest that paternal care plays an important role in the maintenance of male egg carrying in this species. In addition, the methodology developed may become useful in determining true genetic parents in other species in which neither the father nor the mother can be determined by observational methods.     

Paternity and egg cannibalism in the ringlegged earwig Euborellia annulipes (Dermaptera: Anisolabididae)

Cannibalism is a common occurrence in nature, and many cannibals prey on relatively small and defenseless life stages, such as eggs or young juveniles. Such behavior provides many benefits to the cannibal, but cannibalistic individuals also face risks, including the cost of decreasing their inclusive fitness by eating close relatives such as siblings or offspring. This risk can be mitigated if cannibals can recognize and avoid preying on kin. Here, we tested whether male ringlegged earwigs Euborellia annulipes avoid cannibalizing eggs that they had sired. In this species, females care for their own eggs, but males provide no care and frequently prey upon eggs. We found that when presented with an unguarded clutch of eggs, male earwigs nearly always cannibalized some eggs, but that the proportion of eggs eaten was smaller if the male had sired the clutch. This suggests that males can distinguish between their own offspring and unrelated offspring and that they avoid harming their kin.     

Rice water weevil females of different elytral color morphs: comparisons of locomotor activity, mating success, and reproductive capacity

Females and males of the rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Erirhinidae), have two elytral color morphs in Texas: the central pattern of their elytra is black (dark morph) or gray (light morph). In southeast Texas, the dark and light females exhibited similar proportions (28.6 and 32.0%, respectively) in populations collected during the spring. In this study, females of the two morphs were collected near rice fields in southeast Texas during April and May 2005. In the laboratory, light females were more active than dark ones. They mated equally successfully with males, irrespective of morph. For females supplied with males for 2 d or kept solitary, and then reared on rice seedlings for 48 d, no significant differences were found between the two morphs in oviposition period, number of eggs deposited, and survival rate. In both morphs, a proportion of mated females did not oviposit throughout the rearing period, implying that a mating experience might be necessary before reproductive development can be initiated. However, oviposition occurred in a proportion of females in which no mating experience could be detected, and their eggs produced larvae, which suggests the probability of existing parthenogenetic females in southeast Texas.     

Functional infertility among territorial males in two passerine species, the willow warbler Phylloscopus trochilus and the bluethroat Luscinia svecica

Information about male infertility in free-living birds is scarce, but anecdotal and circumstantial evidence suggests that it does occur regularly at a low frequency. In this paper we document three cases of azoospermia in two passerine species, the willow warbler Phylloscopus trochilus and the bluethroat Luscinia svecica at their breeding grounds in South Norway. In willow warblers, two males out of a sample of 50 territory holders had no sperm in their seminal glomera, the storage site of sperm ready for ejaculation. The two males also had very small testes. One out of 48 bluethroat males also had no sperm in the seminal glomera. This male had an extreme asymmetry of the testes, with the right testis being about twice as large as the left. He also failed to fertilize any eggs in his own nest, as well as in neighbouring nests, as revealed by microsatellite genotyping. Thus, the proportion of males without sperm seems to be at a magnitude of a few (2–4) percent in both species. These are among the first estimates of the frequency of azoospermia in wild birds. Our results indicate a significant risk for sexually monogamous females of laying unfertilized eggs, which could favour the evolution of extra-pair copulation as a fertility insurance strategy in females.     

Faint lined (Fnl): a novel X-linked coat mutant in the mouse

We report here a novel X-linked mutant, named faint lined (Fnl), which was discovered in the litter of an irradiated 3H1 male (Dr Bruce Cattanach, personal communication). The mutation is associated with fine dorsal striping in affected heterozygous females and prenatal lethality in males. Approximately 50% of Fnl/+ females die in utero and surviving animals have a reduced weight at birth and weaning. Histological studies failed to reveal the underlying basis of the phenotype or any gross structural abnormalities in internal organs (Fnl/+ x Mus spretus) F1 affected females were backcrossed to 3H1 males and haplotype analysis positioned Fnl in the proximal region of the mouse X chromosome distal to Ant2 and proximal to Hprt. Therefore, Fnl lies within a defined conserved segment and its human homologue can be predicted to lie in the ANT2-HPRT region in Xq25. Further genetic resolution of co-segregating markers flanking Fnl established that Fnl lies in a 7.6 +/- 2.6 cM interval between DXMit50 and DXMit82.     

Strong allelic association between the torsion dystonia gene (DYT1) and loci on chromosome 9q34 in Ashkenazi Jews

The DYT1 gene responsible for early-onset, idiopathic torsion dystonia (ITD) in the Ashkenazi Jewish population, as well as in one large non-Jewish family, has been mapped to chromosome 9q32-34. Using (GT)n and RFLP markers in this region, we have identified obligate recombination events in some of these Jewish families, which further delineate the area containing the DYT1 gene to a 6-cM region bounded by loci AK1 and ASS. In 52 unrelated, affected Ashkenazi Jewish individuals, we have found highly significant linkage disequilibrium between a particular extended haplotype at the ABL-ASS loci and the DYT1 gene. The 4/A12 haplotype for ABL-ASS is present on 69% of the disease-bearing chromosomes among affected Jewish individuals and on only 1% of control Jewish chromosomes (chi 2 = 91.07, P much less than .001). The allelic association between this extended haplotype and DYT1 predicts that these three genes lie within 1-2 cM of each other; on the basis of obligate recombination events, the DYT1 gene is centromeric to ASS. Furthermore, this allelic association supports the idea that a single mutation event is responsible for most hereditary cases of dystonia in the Jewish population. Of the 53 definitely affected typed, 13 appear to be sporadic, with no family history of dystonia. However, the proportion of sporadic cases which potentially carry the A12 haplotype at ASS (8/13 [62%]) is similar to the proportion of familial cases with A12 (28/40 [70%]). This suggests that many sporadic cases are hereditary, that the disease gene frequency is greater than 1/15,000, and that the penetrance is lower than 30%, as previously estimated in this population. Most affected individuals were heterozygous for the ABL-ASS haplotype, a finding supporting autosomal dominant inheritance of the DYT1 gene. The ABL-ASS extended-haplotype status will provide predictive value for carrier status in Jewish individuals. This information can be used for molecular diagnosis, evaluation of subclinical expression of the disease, and elucidation of environmental factors which may modify clinical symptoms.     

X-chromosome inactivation and mutation pattern in the Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinemia. Italian XLA Collaborative Group

BACKGROUND: The diagnosis of X-linked agammaglobulinemia (XLA) is not always clearcut. Not all XLA conform to the classic phenotype and less than 50% of affected boys have a family history of immunodeficiency. Mutations in the gene for Bruton's tyrosine kinase (BTK) are responsible for the majority of agammaglobulinemia cases. However, a certain proportion of patients may have mutations involving other genes, although they show with an XLA phenotype. We performed BTK gene mutation analysis in 37 males with presumed XLA and analyzed the pattern of X-chromosome inactivation (XCI) in 31 mothers to evaluate the relevance of these approaches to diagnosis and genetic counseling. MATERIALS AND METHODS: Twenty affected males with a sporadic occurrence and 17 familial cases belonging to nine families were enrolled within the framework of the Italian Multicenter Clinical Study on XLA. We used non-isotopic RNase cleavage assay (NIRCA), followed by cDNA sequence determination to screen for BTK mutations and X-chromosome inactivation analysis for carrier detection. RESULTS: Using the cDNA-based approach, the identification of BTK gene abnormalities confirmed the clinical diagnosis of XLA in 31 of 37 affected infants. Missense was the most frequent mutational event and the kinase domain was mostly involved. In addition, nine novel mutations were identified. In sporadic cases, BTK gene abnormalities were identified in 9 out of 10 patients whose mothers had a nonrandom pattern of XCI and in 5 out of 6 patients whose mother had a random pattern of XCI. With the exception of one family, all patients with a familial occurrence and born to mothers with a nonrandom pattern of XCI had mutations of the BTK gene. CONCLUSIONS: Our findings indicate that in sporadic cases BTK gene sequencing is the only reliable tool for a definitive diagnosis of XLA and support XCI as the first diagnostic tool in the mothers of affected males in multiple generations. Furthermore, our molecular analysis confirms that 10-20% of BTK-unaltered patients have disorders caused by defects in other genes.     

Mutations in btk in patients with presumed X-linked agammaglobulinemia.

In 1993, two groups showed that X-linked agammaglobulinemia (XLA) was due to mutations in a tyrosine kinase now called Btk. Most laboratories have been able to detect mutations in Btk in 80%-90% of males with presumed XLA. The remaining patients may have mutations in Btk that are difficult to identify, or they may have defects that are phenotypically similar to XLA but genotypically different. We analyzed 101 families in which affected males were diagnosed as having XLA. Mutations in Btk were identified in 38 of 40 families with more than one affected family member and in 56 of 61 families with sporadic disease. Excluding the patients in whom the marked decrease in B cell numbers characteristic of XLA could not be confirmed by immunofluorescence studies, mutations in Btk were identified in 43 of 46 patients with presumed sporadic XLA. Two of the three remaining patients had defects in other genes required for normal B cell development, and the third patient was unlikely to have XLA, on the basis of results of extensive Btk analysis. Our techniques were unable to identify a mutation in Btk in one male with both a family history and laboratory findings suggestive of XLA. DNA samples from 41 of 49 of the mothers of males with sporadic disease and proven mutations in Btk were positive for the mutation found in their son. In the other 8 families, the mutation appeared to arise in the maternal germ line. In 20 families, haplotype analysis showed that the new mutation originated in the maternal grandfather or great-grandfather. These studies indicate that 90%-95% of males with presumed XLA have mutations in Btk. The other patients are likely to have defects in other genes.     

A gene that modifies the sex ratio in a bisexual strain of Sciara ocellaris.

The influence of an X-linked recessive mutation, sepia, on the sex determination of a bisexual strain of Sciara ocellaris was studied. It induces an alteration in the sex ratio, especially in the progeny of heterozygous females, increasing the proportion of males. These results cannot be explained by differential fecundity of the female parents of different genotypes nor by differential mortality between the sexes. The occurrence of gynandromorphs indicates that the mutant probably interferes with the processes of X-chromosome elimination. Observations that heterozygous females which received the sepia allele from their mothers produced a higher frequency of gynandromorphs than females which received the mutated allele from their male parents, suggest that the mutation is interfering with the mechanism of chromosome elimination present in the egg cytoplasm.