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PubMed1998

Geneticists share the family jewels: how inbreeding has contributed to understanding hereditary skin disease.

BACKGROUND: Offspring resulting from consanguineous marriages have been important in advancing research in genodermatoses. OBJECTIVE: The concepts of consanguinity and inbreeding are reviewed and their contributions to research in hereditary skin diseases explained. METHODS: Examples are given in which inbred individuals with hereditary skin disease have increased our knowledge of skin disease genetics. RESULTS: An enhanced understanding of the genetics of xeroderma pigmentosum, lamellar ichthyosis, and Werner's syndrome, among others, has arisen from the observation of populations and families in which inbreeding has occurred. CONCLUSION: Populations practicing inbreeding and consanguineous marriages in generally outbred populations have provided important observations for determining the inheritance pattern of several genodermatoses and for identifying the responsible genes.

Consanguinity↗
PubMed1985

Academic inbreeding in nursing: intentional or inevitable?

Consensus exists that academic inbreeding inhibits innovation and scholarly achievement. Nevertheless, schools of nursing have been--and continue to be--more inbred than other schools within the university. In a follow-up survey to Miller and Ehnes' 1977 study, inbreeding has increased slightly--more junior than senior faculty are inbred, and rapidly expanding schools are the most inbred. A comparison of two schools (one highly inbred and one less so) demonstrates that schools do not recruit faculty from other schools in their region. The paper concludes that economic pressures may force deans to hire their own graduates (reducing recruitment costs) for junior positions and pay a relatively larger sum for a few senior level outbred faculty. Thus, academic inbreeding in nursing may be both inevitable and intentional.

Education, Nursing, Graduate↗
PubMed2026

Long-term small effective population size, inbreeding, and a recessive lethal haplotype drive premature death in the endangered Devils Hole pupfish (Cyprinodon diabolis).

As anthropogenic habitat fragmentation and population decline accelerate globally, growing numbers of species face compounding demographic and genetic threats to long-term survival. Many populations are already forced to persist at chronically small sizes, yet the genomic and fitness consequences of this fate remain poorly understood. Here we leverage the demographic history of the Devils Hole pupfish to investigate how long-term small population size and recent bottlenecks have shaped genetic diversity, genetic load, inbreeding, and fitness through comparative population genomics, historical sequencing, and sampling embryos that died prematurely during development. We find that genetic diversity in Devils Hole pupfish is among the lowest recorded in the wild and that fixed load is high, consistent with thousands of generations of isolation at small population size. Even in the face of this low diversity and high fixed load, we show that inbreeding is still strongly associated with premature embryonic death, which affects up to 25% of offspring in the captive refuge and can be identified in advance based on a characteristic elongated heart tube and reduced heart rate. We discovered a recessive lethal haplotype segregating at ~20% frequency that accounts for 50% of embryonic deaths and contains mutations in MIB1 and MMP16, genes associated with cardiomyopathy and atrial fibrillation. Our findings link genotype, phenotype, and fitness in an iconic endangered species to provide a rare comprehensive view into the evolutionary dynamics and consequences of long-term small effective population size, demonstrating that endangered species remain vulnerable to inbreeding depression despite extremely low genetic diversity.

Journal Article↗
PubMed2002

Estimation of inbreeding, kinship and genetic distances from surnames--coastal population of middle Dalmatia, Croatia.

This work was dedicated to the investigation of the population structure of the middle Dalmatia settlements: Jesenice, Mimice, Zivogosće and Zaostrog by surname distribution study and applying the isonymous method. The surnames of males and females in marital pairs were analyzed as well as of their first and second-generation ancestors on the sample of a total of 3,024 examinees. The analyses of surnames pointed to the rates of inbreeding, kinship and genetic distances of the populations. Although the values of the inbreeding coefficient are high in all the four settlements, the inbreeding coefficient is exceptionally high in Mimice. A total kinship coefficient for the four settlements speaks also in favor of the high rate of kinship in the examined settlements, i.e. of the high rate of the reproductive isolation of the whole region during the analyzed period. The reasons for such high coefficients are natural features of the examined region (the mountains of Mosor, Biokovo and Rilić), poor traffic connection of this region in the past, the patrilineal mode of inheritance and the demographic specifics of the population. The matrix of genetic distances between examined settlement pairs reveals that Mimice, a settlement with the highest share of isonymous marriages, shows the greatest distances in comparison to the other settlements. On the other hand, Jesenice, Zivogosće and Zaostrog are characterized by small genetic distances, which is the fact that speaks in favor of their genetic homogenization and "openness" toward interpopulational migrations, i.e. the gene flow.

Consanguinity↗
PubMed1991

Note on estimates of the inbreeding coefficient through study of pedigrees and isonymous marriages.

Crow and Mange (1965) developed a method to estimate the inbreeding coefficient (F) through an ingenious surname analysis. Such formulations assume a regularity of transmission of surnames, monophyletism, and random occurrence of consanguineous marriages. Accordingly, the ratio of isonymous partners to F of the offspring is equal to 4. Nevertheless, genealogy analyses show that the consanguineous marriages do not necessarily occur regularly. Therefore the isonymy analysis gives a misestimation of the inbreeding coefficient, depending on the prevailing form of nonrandomness. We suggest a small correction to the formulation in situations when pedigree information is available. The weighted mean of the ratio of isonymous partners to F of the known consanguineous marriages is suggested as a way to improve the formulas. The technique was applied to a northeastern Brazilian sample, and the results agree well with those of bioassays and therefore provide an apparently more realistic estimate of the inbreeding coefficient by isonymy.

Brazil↗
PubMed1981

Inbreeding secular changes in the Riomaggiore and Silla Valleys, Italy, from 1565 to 1980.

Variations in the frequency of consanguineous marriages and inbreeding secular changes have been examined in an Italian mountain population from 1565 up to 1980. Wide microgeographic differences in inbreeding values related to the different altitude of the villages and their geographic location have been detected. A close parallelism between demographic variations and inbreeding secular changes has been pointed out. The dependence of the frequency increase in first cousin marriages observed in the second half of the XIX cent. On the increase in sibship size is suggested.

Altitude↗
PubMed1997

[Increase in the effectiveness of using inbreeding in pedigree stocks of dairy cattle].

At the main Russian bloodstock farms improving Black-Pied cattle, the influence of inbreeding level on pedigree and reproductive characteristics of animals was studied. Inbreeding patterns with the highest selective effect were revealed. Mothers were found to have an increased effect on milk productivity of daughters obtained from close inbreeding. Recommendations for improving breeding strategy are given.

Animal Husbandry↗
PubMed1997

Inbreeding in Escazú, Costa Rica (1800-1840, 1850-1899): isonymy and ecclesiastical dispensations.

We investigate the inbreeding levels in Escazú, Costa Rica, during 1800-1840 and 1850-1899. Inbreeding was researched through analysis of ecclesiastical dispensations and by two isonymy methods (Crow and Mange 1965; Pinto-Cisternas et al. 1985). As expected, the dispensation inbreeding coefficients were lower than those obtained through isonymy. However, the three methods indicate that consanguinity increased in the community during the second part of the nineteenth century.

Anthropology↗
PubMed1998

Ethnohistorical evidence for inbreeding among the pre-Hispanic Mixtec royal caste.

Pre-Columbian Mixtec social organization was distinguished by the tight endogamy of the ruling class, which included many consanguineous marriages. It was also characterized by a vigorous historical and genealogical tradition. The historical documents, or codices, provide materials for the calculation of the levels of inbreeding present before the Spanish Conquest. A genealogical analysis of inbreeding was performed on the combined pedigree, which spanned the tenth through sixteenth centuries, of all individuals connected by ancestry, descent, or marriage with Lord 8 Deer Jaguar Claw of Tilantongo (A.D. 1063-1115). Sixty of the 217 couples (27.65%) were consanguineous. When only couples of wholly known grandparentage were considered (N = 39), F = 0.1051. The mean F of all couples, even those where one spouse was of unknown parentage, was 0.0243. Over the 550 years of the pedigree the maximum F in any 52-year period was 0.1324. This level of inbreeding is sufficient to produce noticeable effects on population structure and affinities over time.

Consanguinity↗
PubMed2002

Inbreeding in Littledale's whistling rat Parotomys littledalei.

Despite its rarity in nature, inbreeding is sometimes evident in species occupying ephemeral, unpredictable habitats, and which occur at low densities. One such species is Littledale's whistling rat, Parotomys littledalei, a murid rodent endemic to the south-west arid region of South Africa. Using a captive population of P. littledalei, I studied mate choice for kin and nonkin, and the reproductive performance of inbred and outbred pairs. In choice tests, estrous females presented with either odors or actual males showed a preference for siblings or half-siblings to unrelated males. Males did not discriminate between the odor of estrous kin and nonkin. In breeding studies, inbred (mother-son; brother-sister) and outbred (proven female and an unrelated young male and nonsiblings) pairs had a similar reproductive output, although the sex ratio favored males in inbred litters. The development of inbred young was indistinguishable from outbred young. The results indicate that female P. littledalei prefer to inbreed, but there are no apparent advantages to inbreeding over outbreeding.

Animals↗
PubMed1985

Developmental mutants isolated from wild-caught Xenopus laevis by gynogenesis and inbreeding.

Xenopus laevis obtained from indigenous African populations are a rich source of mutants affecting development. Gynogenesis and inbreeding were used to isolate mutants affecting development from wild-caught Xenopus laevis females. Fourteen mutants were recovered from eight females tested. One mutant was recovered from each of two females. This load of 1.875 developmental mutants per female is similar to that found in the axolotl (Ambystoma mexicanum), a urodele amphibian, and is only slightly less than the load of mutants with major developmental effects found in Drosophila and man. These results suggest that the anuran amphibian Xenopus laevis, an ancestrally tetraploid species, has undergone extensive diploidization of developmentally important loci and that gynogenesis and inbreeding of wild-caught animals can provide adequate mutants at diploid loci for developmental genetic studies.

Animals↗
PubMed2003

Inbreeding, maternal care and genomic imprinting.

Inactivation of expression of the paternal allele at two maternally silent imprinted loci has recently been reported to diminish the quality of care that female mice lavish on their offspring. This suggests that there can be disagreement between the maternally and paternally derived genomes of mothers over how much care for offspring is appropriate, with the paternally derived genome favoring greater care. The reason for such disagreement is not obvious because the maternally and paternally derived alleles at a locus have equal probabilities of being transmitted to each of the mother's ova and, therefore, would appear to have equal interests in a mother's offspring. However, if a female mates with a related male, her two alleles may have different probabilities of being present in the sperm that fertilize her ova. Natural selection can favor silencing of the maternally derived allele at a locus that enhances the quality of maternal care if the average patrilineal relatedness between a female and her mates decreases more rapidly than the average matrilineal relatedness. Just such an asymmetrical decrease in relatedness over time would be expected in a structured population in which patrilineal inbreeding is more common than matrilineal inbreeding.

Animals↗
PubMed1994

The interaction of inbreeding depression and environmental stochasticity in the risk of extinction of small populations.

Current population genetic and population dynamic models are inappropriate to judge the risk of extinction of small populations due to the combined effects of inbreeding, genetic drift, demographic stochasticity, and environmental stochasticity. Instead, a model based on the aggregated fates of individuals is advocated. The unequal distribution of resources over individuals is an essential part of this model. The model allows the incorporation of the mutation-selection dynamics of alleles leading to inbreeding effects and to fixation of slightly deleterious mutations as a result of genetic drift. The slightly deleterious mutations lower the conversion of resources into offspring. Whereas lethal alleles are rapidly eliminated by selection in small populations, the selection against mild deleterious effects depends strongly on effective population size and on the social system, that is, on the division of resources among individuals. The model allows for the study of rates at which processes occur while far away from equilibrium, which is crucial in understanding the extinction risks of threatened populations. One example of the latter is illustrated in simulations in which small populations become extinct between approximately 100 and 200 generations after they became small populations, due to a gradual accumulation of mildly deleterious mutations.

Alleles↗
PubMed1975

Power of assaying inbreeding through sampling of phenotypes and mating types.

Power of detecting inbreeding coefficient through a phenotype or mating type bioassay is evaluated as a function of sample size and level of inbreeding. Efficiency of a mating bioassay over a phenotypic one is then defined as the ratio of the two power functions for a given sample size while surveying the same population (i.e., with the same F). Empirical analysis of this efficiency function indicates that efficiency depends largely on n and F apart from the gene frequencies at the locus.

Alleles↗
PubMed1979

Inbreeding and heterogamic mating: an alternative to Averhoff and Richardson.

An alternative explanation to the pheromonal control of mating through chemoreceptor saturation proposed by Averhoff and Richardson (1974) is offered for the apparent rise in heterogamic mating in their experiments, after several generations of full-sib mating. In a multiple-choice mating between two genotypic strains differing in their level of sexual vigor, there is a sequence from heterogamic to homogamic mating. It is proposed that, by reducing mating speed, inbreeding changes the rate of this sequence but not its pattern, so the apparent level of heterogamic mating will increase during inbreeding, for a fixed observation period. This hypothesis was tested using the Kence-Bryant model of mating success.

Animals↗
PubMed2003

Change in frequency of a rare mutant allele: a general formula and applications to partial inbreeding models.

We deduce and prove a general formula to approximate the change in frequency of a mutant allele under weak selection, when this allele is introduced in small frequency into a population which was previously at a fixation state. We apply the formula to autosomal genes in partial selfing models and to autosomal as well as sex-linked genes in partial sib mating models. It is shown that the fate of a rare mutant allele depends not only on the selection parameters, the inbreeding coefficient and the reproductive values of the sexes in sex-differentiated populations, but also on coefficients of relatedness between mates. This is interpreted as a kin selection effect caused by inbreeding per se.

Alleles↗
PubMed2002

Influences of inbreeding and genetics on telomere length in mice.

We measured telomere lengths of blood leukocytes in several inbred and outbred mammalian species, using a telomere-specific fluorescent probe and flow cytometry. Humans, non-human primates, and three outbred populations of Peromyscus mice ( Peromyscus leucopus, Peromyscus maniculatus, and Peromyscus polionotus) have short telomeres. Two common strains of laboratory mice, C57BL/6J and DBA/2J, have telomeres several times longer than most other mammals surveyed. Moreover, the two inbred laboratory mouse strains display significantly different telomere lengths, suggesting the existence of strain-specific genetic determinants. To further examine the effects of inbreeding, we studied three Peromyscus leucopus inbred lines (GS109, GS16A1, and GS16B), all derived from the outbred P. leucopus stock. Telomeres of all three inbred lines are significantly lengthened relative to outbred P. leucopus, and the three lines display strain-specific significantly different telomere lengths, much like the C57BL/6J and DBA/2J strains of M. musculus. To further characterize the genetic inheritance of telomere length, we carried out several crosses to obtain hybrid F(1) mice between parental strains displaying the phenotype of long and short telomeres. In all F(1) mice assayed, peripheral blood leukocyte telomere length was intermediate to that of the parents. Additionally, we generated F(2) mice from a cross of the ( P. leucopus outbred x GS16B)F(1). Based on the distribution of telomere length in the F(2) population, we determined that more than five loci contribute to telomere length regulation in Peromyscus. We concluded that inbreeding, through unknown mechanisms, results in the elongation of telomeres, and that telomere length for a given species and/or sub-strain is genetically determined by multiple segregating loci.

Animals↗
PubMed2005

Inbreeding depression of female fecundity by genetic factors retained in natural populations of a male-haploid social mite (Acari: Tetranychidae).

We previously determined that certain recessive genes decrease female fecundity in a haplo-diploid spider mite, Stigmaeopsis miscanthi (Saito). However, whether the depression was caused by the breakdown of heterosis or the expression of deleterious genes retained in a population could not be determined, because we had started our inbreeding experiment from a mixture of two isolated populations. In order to answer this basic question, inbreeding effects on survival and fecundity were measured for eight small populations occurring far from the two initial populations. There was little depression of immature survival of inbred lineages in all populations. On the other hand, in two inbred lineages, both originating from the smallest populations, female oviposition decreased significantly with the increase of Wrights f-value, showing that mildly deleterious genes are actually retained even in natural populations of haplo-diploid organisms.

Animals↗