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PubMed1980

The spectrum of frontonasal dysplasia in an inbred pedigree.

An inbred pedigree is described in which three members were affected with FND (Frontonasal Dysplasia). Two of these individuals were products of a consanguineous mating with an inbreeding coefficient of F = 0.0391. The third affected individual (propositus), was born to a marriage in which the coefficient of inbreeding was 0.0742. The mother of the propositus, whose inbreeding coefficient was 0.0625, had borderline hypertelorism and a broad nose. Several other members of the pedigree who had hypertelorism were products of consanguineous matings. The presence of consanguinity in all individuals affected with a variety of manifestations of FND suggests a genetic mechanism for this malformation.

Consanguinity↗
PubMed2006

Ignoring distant genealogic loops leads to false-positives in homozygosity mapping.

Distant consanguineous loops are often unknown or ignored during homozygosity mapping analysis. This may potentially lead to an increased rate of false-positive linkage results. We show that failure to take into account the distant loops may seriously underestimate the degree of consanguinity, especially for people from genetically isolated populations; in 6 Alzheimer's disease (AD) patients the distant loops accounted for 57.7 % of inbreeding on average. Theoretical evaluation showed that ignoring distant loops, which account for 18-75% of inbreeding, inflates the frequency of false positive conclusions substantially in 2-point linkage analysis, up to several hundred times. In multipoint linkage analysis of the 6 AD patients a chromosome-wide "empirical" significance of 5% corresponded to a true false positive rate of 11.1%. We show that converting multiple loops to a hypothetical loop capturing all inbreeding may be a convenient solution to avoid false positive results. When extended genealogic data are not available a hypothetical loop may still be constructed based on genomic data.

Alzheimer Disease↗
PubMed1967

Addiction liability of albino rats: breeding for quantitive differences in morphine drinking.

Selective breeding produced two strains of rats that differ in their susceptibility to morphine addiction. Inbreeding the more susceptible rats in an unselected population produced susceptible offspring; inbreeding resistant rats produced resistant offspring. Further selection and inbreeding increased the strain difference in the F(2) and F(3) generations. The F(3) generation also differed in their susceptibility to alcohol addiction.

Alcoholism↗
PubMed2003

A new obesity-prone, glucose-intolerant rat strain (F.DIO).

Previous breeding for the diet-induced obese (DIO) trait from outbred Sprague-Dawley rats produced a substrain with selection characteristics suggesting a polygenic mode of inheritance. To assess this issue further, selectively bred DIO male rats were crossed with obesity-resistant inbred Fischer F344 dams. Male offspring were crossed twice more against female F344 dams. The resultant N3 (F.DIO) rats were then inbred three more times. On low-fat chow, 10-wk-old male and female DIO rats weighed 86 and 59% more than respective F344 rats. By the N3 (F.DIO) generation, they were only 12 and 10% heavier, respectively. After three additional inbreeding cycles, chow-fed F.DIO males had an exaggerated insulin response to oral glucose compared with F344 rats. After 3 wk on a 31% fat (high-energy) diet, male N3 F.DIO rats gained 16-20% more carcass and adipose weight with 98% higher plasma leptin levels, whereas F.DIO females gained 36-54% more carcass and adipose weight with 130% higher leptin levels than comparable F344 rats. After three inbreeding cycles, F.DIO males still gained more weight on high-energy diet and developed a threefold greater insulin response to oral glucose than F344 males. Preservation of the DIO and glucose intolerance traits through successive backcrosses and inbreeding cycles to produce the F.DIO strain lends further support to the idea that they inherited in a polygenic fashion.

Animals↗
PubMed2005

Simulation-based homozygosity mapping with the GAW14 COGA dataset on alcoholism.

BACKGROUND: We have developed a simulation-based approach to the analysis of shared homozygous chromosomal segments and have applied it to data on allele sharing among alcoholics in a single Collaborative Study on the Genetics of Alcoholism pedigree. Our assessment of sharing involved the use of a single-nucleotide polymorphism (SNP) marker map provided by Affymetrix. RESULTS: All 11 affected individuals in the selected pedigree shared 2 copies of an allele at 4 adjacent SNPs in a region on chromosome 5. Via simulation, we determined that the probability that such sharing is caused by mere chance is less than 0.0000001. After correcting for undocumented inbreeding, this probability rose to 0.0016. The probability that the shared segment emanates from a single ancestor and is unrelated to the affection status is less than 0.0000001 in the corrected pedigree. Haplotype association analysis and a search for a protective locus using unaffected individuals yielded no significant results. CONCLUSION: Homozygosity mapping results on chromosome 5 provide suggestive evidence of the region's role as one that may harbor a genetic determinant of alcoholism. Furthermore, the probabilities of chance homozygous allele sharing for the original and for the inbreeding-corrected pedigree provide insight into the impact that inbreeding can have on such calculations.

Alcoholism↗
PubMed2001

Consanguineous marriage among the Fulani.

The Fulani are a broad ethnic category of nomadic and seminomadic pastoralists and agropastoralists living in the semiarid Sahel region of sub-Saharan Africa. The Fulani are patrilineal, patrilocal, and moderately polygynous, with arranged first marriages accompanied by the payment of bridewealth, ideally in the form of cattle. Consanguineous marriage is frequent, with first or second cousin marriage preferred. In this paper we present data on levels of consanguineous marriage among the Fulani of northern Burkina Faso and test the hypothesis that inbreeding may be more frequent when there is a scarcity of cattle available, since bridewealth demands are thought to be reduced with close-kin marriage. Among 308 women's marriages, 203 (65.8%) were between kin up to and including second cousins, and 102 (33.1%) were between nonkin. Among 276 men's marriages, 196 (71.0%) were between kin up to and including second cousins, and 77 (27.9%) were between nonkin. The mean population inbreeding coefficient (alpha) was 0.0355 for women, and 0.0374 for men. No increase was found in population levels of inbreeding estimated from marriages contracted after the droughts of 1973 and 1984, which drastically reduced the Fulani's cattle stocks. However, a significantly higher rate of consanguineous marriage was found in families owning the fewest cattle.

Animal Husbandry↗
PubMed2002

Consanguinity in Spain: socioeconomic, demographic, and geographic influences.

Information on consanguinity in Spain was reanalyzed in order to obtain a more complete picture of consanguinity patterns by considering temporal, geographical, demographic, and economic factors. To obtain data on consanguineous marriages, we reviewed 106 published references. Only populations with homogeneous geographical characteristics, economic activities, transportation facilities, and the like, were considered. Two-way analysis of variance (ANOVA) provided highly significant differences (p < 0.001) for a both for time periods and for urban versus rural patterns, but there was no interaction between the latter two. A regression analysis shows that for rural areas the geographic characteristics, economy, communications, and index of demographic tendency were significant predictors of the inbreeding coefficient. The results obtained indicate that urban and rural patterns differ significantly and that the temporal factor needs to be taken into account before comparing inbreeding coefficients. In urban areas the census size and altitude are included in the regression equation as significant variables, but association was not found between alpha and the index of demographic tendency (population increase or decrease). Instead, the absolute number of inhabitants (census size) was significant. In rural areas geographic characteristics, communications, and index of demographic tendency were significant predictors of the inbreeding coefficient.

Analysis of Variance↗
PubMed2001

Maternal effect genes and the evolution of sociality in haplo-diploid organisms.

Maternal care and female-biased sex ratios are considered by many to be essential prerequisites for the evolution of eusocial behaviors among the hymenoptera. Using population genetic models, I investigate the evolution of genes that have positive maternal effects but negative, direct effects on offspring fitness. I find that, under many conditions, such genes evolve more easily in haplo-diploids than in diplo-diploids. In fact, the conditions are less restrictive than those of kin selection theory, which postulate genes with negative direct effects but positive sib-social effects. For example, the conditions permitting the evolution of maternal effect genes are not affected if females mate multiply, whereas multiple mating reduces the efficacy of kin selection by reducing genetic relatedness within colonies. Inbreeding also differentially facilitates evolution of maternal effect genes in haplo-diploids relative to diplo-diploids, although it does not differentially affect the evolution of sib-altruism genes. Furthermore, when the direct, deleterious pleiotropic effect is restricted to sons, a maternal effect gene can evolve when the beneficial maternal effect is less than half (with inbreeding, much less) of the deleterious effect on sons. For kin selection, however, the sib-social benefits must always exceed the direct costs because genetic relatedness is always less than or equal to 1.0. The results suggest that haplo-diploidy facilitates (1) the evolution of maternal care, and (2) the evolution of maternal effect genes with antagonistic pleiotropic effects on sons. The latter effect may help explain the tendency toward female-biased sex ratios in haplo-diploids, especially those with inbreeding. I conclude that haplo-diploidy not only facilitates the evolution of sister-sister altruism by kin selection but also facilitates the evolution of maternal care and female-biased sex ratios, two prerequisites for eusociality.

Alleles↗
PubMed1992

Structure of breeding programs to capitalize on reproductive technology for genetic improvement.

Potential rates of genetic progress are limited by biological constraints, which along with genetic parameters determine the structure of breeding programs to be employed for maximum genetic improvement. The objective here is to determine whether current progeny-testing programs in dairy cattle, which have been dictated and constrained by low female reproductive rates, need to be changed to capitalize on new reproductive technologies and how these changes should be implemented. Many differences between breeding programs diminish when selection on animal model genetic evaluations across all age and population groups is adopted as a strategy. Progeny-testing schemes then evolve toward dispersed open nucleus breeding schemes when multiple ovulation and embryo transfer is used on bull-dams. Nucleus breeding schemes have been advocated to capitalize on embryo transfer technology. In nucleus breeding schemes utilizing high reproductive rates, inbreeding, rather than reproductive rate, poses a limit to genetic progress, and strategies that maximize response to selection while limiting inbreeding need to be employed. One strategy is mating each dam to several sires rather than only one sire. In vitro embryo production techniques can be used to facilitate such mating strategies. Large-scale in vitro embryo production programs, in which large numbers of embryos per female are tested in the commercial population, offer the greatest potential for genetic gain with low rates of inbreeding. Cloning has an impact mainly on methods for dissemination of genetic improvement. Breeding herds, genetically inferior to marketed clones, are needed for continuous genetic gain. Reproductive technologies offer the potential for genetic improvement. Whether new breeding programs require changes in population structure, e.g., by creation of nucleus breeding herds, depends mainly on logistics and on quantity and quality of field information.

Animals↗
PubMed2001

Neither vegetative nor reproductive advantages account for high frequency of male-steriles in southern Spanish gynodioecious Daphne laureola (Thymelaeaceae).

In gynodioecious species, male-steriles (termed "females" hereafter) usually exhibit some reproductive advantage over hermaphrodites that allow them to compensate for the loss of male reproductive function. This compensation can result from higher fecundity, vegetative outperformance, and/or lower inbreeding depression. In this study we compared vegetative and reproductive parameters of female and hermaphrodite Daphne laureola individuals in two southeastern Spanish populations and estimated the magnitude of inbreeding depression up to the seedling emergence stage by conducting controlled pollinations and experimental sowings of seed progenies in the field. Reproductive shrubs of both sexes did not differ significantly in size, leaf production, leaf size, leaf growth, nutrient allocation to leaves, and production of flowers and fruits. Seed set and seed size of cross- and self-pollinated flowers of hermaphrodites and cross-pollinated females were also similar. Seedling emergence rates of self- and cross-pollinated seeds from hermaphrodites under natural field conditions were similar, suggesting a minor role of inbreeding depression up to that reproductive stage. Seeds from females produced more seedlings than selfed seeds from hermaphrodites. In 21 populations surveyed in the study region over a broad geographical and elevational gradient, the proportion of females ranged between 20.6 and 56.1% and was inversely related to elevation. The establishment and maintenance of females in southeastern Spanish populations of D. laureola seem to be mainly mediated by ecological factors.

Journal Article↗
PubMed1992

Genetic disease patterns in Japan: a review.

Comprehensive genetic studies in which the genetic structure of a population is considered against the background of ecological factors, including environmental and social variables, often supply valuable information for the solution of a number of problems in human biology, including reproductive compensation and inbreeding depression. In the first section of this paper we consider the incidence of genetic diseases in Japan in reference to other populations. Some of the genetic disorders found elsewhere do not occur or are of lower frequencies in Japan. On the other hand, a number of genetic diseases occur at higher than usual frequencies, leading to an incidence of genetic disease of the order of about 1 per 100 in newborn Japanese. We next review the studies of consanguinity in Japan and report evidence of very high levels, ranging from 8.6% to 58.0%, for villages during the early part of the twentieth century. The rates are declining rapidly for the country but, because of traditional social values, inbreeding rates remain significant in many small villages. In the final section we consider the probable trends in the frequency of inbreeding on a worldwide basis and point out that frequencies of certain genetic diseases are likely to remain high and even increase in some societies because of various socially prescribed mating patterns.

Consanguinity↗
PubMed2004

Lost in transition--the Island of Susak (1951-2001).

The isolated population of the Island of Susak was thoroughly studied by a multidisciplinary team of the Croatian Academy of Sciences and Arts in early 1950's. Recently, a team of scientists revisited the island. This paper describes the main characteristics of the transition process during which a massive exodus occurred with 90% of the island's population migrating to New Jersey, USA. We summarise the differences in lifestyle, economy, social structure and sense of identity between the historic (1950's) and contemporary (2001) Susak population. We applied contemporary methods (analysis of microsatellite DNA polymorphisms) to investigate local myths about extreme levels of inbreeding and genetic homogeneity among the Susak islanders. Analysis of short-tandem-repeat (STR) loci showed that Susak displayed characteristics of a small homogeneous breeding isolate. The average heterozygosity was found to be low compared to outbred populations. The signature of a recent severe bottleneck could be detected. Analysis of 8 markers located on Xq13-21 in 71 individuals suggested extensive level of linkage disequilibrium (LD). A migrant study was designed to investigate the effects of large environmental changes (Susak vs. USA) and inbreeding (Susak vs. Croatian general population) on some biologically important quantitative traits, such as blood pressure and serum lipids. The results confirmed the positive correlation between inbreeding level and blood pressure that has been reported in the literature on several occasions. The last remnants of this traditional island community will soon be lost forever.

Anthropology↗
PubMed1979

[Population genetics of the population of the European north of the RSFSR. IV. The level of blood relationship in 5 villages of Pinega District, Archangel Province].

Computer program "RODAN-1" is used for inbreeding coefficient estimation. The population studied consists of two communities of 5 villages. 385 marriages were computed. The coefficient of inbreeding is 0.00145 for pedigree for rural Russian population (the Arkhangelsk region). The inverse dependence between a village size and corresponding data of inbreeding coefficient is suggested. An attempt was undertaken to estimate the genealogical information value for each pedigree and average information value for a village.

Arctic Regions↗
PubMed2005

Parental consanguinity and risk of breast cancer: a population-based case-control study.

BACKGROUND: An estimated 600 million people in the world have consanguineous parents. The effect of consanguinity on the risk of breast cancer is uncertain. The objective of this case-control study was to examine whether parental consanguinity and different levels of inbreeding affect the risk and pathology characteristics of breast cancer. MATERIAL/METHODS: Over a 36-month period, consecutive female breast cancer patients were recruited in the main cancer hospital in the United Arab Emirates. All were locally born Arabs with a tissue diagnosis of breast cancer. The controls were locally born Arabs without breast cancer matched to cases by sex, age, and residence. The coefficient of inbreeding (F) of both groups was determined from information they provided about their parents' kinship. RESULTS: The mean age of the 72 patients and 187 controls was 48.6 years (range: 25-86) and 48.5 years (range: 25-82), respectively (P = 0.46). Consanguinity rates of the patients and controls were 29.2% and 28.9% (P = 0.96) and the coefficients of inbreeding were 0.0117 and 0.0167 (P = 0.21), respectively. More closely inbred women (F > or = 0.0625) were less frequent among patients than controls, but the difference was not statistically significant (P = 0.12). The rates of pathological stage of disease, tumor histologies, and tumor grades were similar between more and less inbred patients. CONCLUSIONS: Parental consanguinity in Arabs, even when a marriage is between first cousins or double first cousins, was not associated with an altered risk of breast cancer.

Adult↗
PubMed2006

The fitness effects of outcrossing in Calylophus serrulatus, a permanent translocation heterozygote.

Small and relatively isolated populations that occupy fragmented habitat are at risk of local extinction. However, fitness consequences of fragmentation related to mating distance, such as inbreeding depression following increased self- and near-neighbor mating, may not follow standard expectations in species with specialized genetic systems. We investigated the effect of mating distance on progeny fitness in Calylophus serrulatus, a primarily autogamous, permanent translocation heterozygote that is restricted to prairie fragments in the North American tallgrass prairie region. We pollinated flowers by hand in the field with pollen sampled at various distances from the maternal parent within and between three populations in southeastern Minnesota. We raised the progeny in a greenhouse and measured fitness-related characters. Because their genetic system prevents loss of heterozygosity throughout much of the genome, regardless of inbreeding, permanent translocation heterozygotes are not expected to exhibit inbreeding depression. Consistent with this expectation, in no case did progeny of self matings suffer significantly reduced mean fitness compared to progeny from crosses between plants. Crosses between plants in the two closely situated (2 km) populations yielded progeny with fitness intermediate to their parents, but crosses between each of those populations and the more distant (20 km) population yielded progeny with reduced fitness, suggesting outbreeding depression at this largest spatial scale. Similarly, fitness of self-pollinated progeny and progeny from "near" crosses (<2 m) within populations tended to be higher than "mid" (10-25 m) and "far" (>35 m) cross-progeny fitness. Under the current conditions of fragmentation, it seems likely that the distant matings that produce outbreeding depression are rare. It appears that mean fitness in this species is maintained in the context of severe fragmentation of its populations, largely because of its genetic system.

Crosses, Genetic↗
PubMed2006

[Dynamics of allozyme heterozygosity in Siberian dwarf pine Pinus pumila (Pall.) Regel populations of the Russian Far East: comparison of embryos and maternal plants].

Siberian dwarf pine, or Japanese stone pine, Pinus pumila (Pall.) Regel is widespread in eastern Siberia and the Russian Far East; the species is bird-dispersed and has a unique spreading or shrub living form. A mixed mating system (predominant outcrossing with self-pollination and matings of close relatives) leads to the formation of partly inbred progenies in P. pumila, as in the majority of other conifers. The question arises as to whether inbred individuals persist in the reproductive part of a population, which can have negative genetic consequences. The ADH, FDH, FEST, GDH, GOT, IDH, LAP, MNR, MDH, PEPCA, 6-PGD, PGI, PGM, SKDH, and SOD isozyme systems were analyzed to study the dynamics of heterozygosity in four P. pumila natural populations from the Pacific region, optimal for the species. Samples were collected in northern Koryakia, southern Kamchatka (two samples), and the Kunashir Island (Kurils). Wright's fixation index was used to estimate the level of inbreeding in embryos from dormant seeds resulting from free pollination and in maternal plants. A substantial level of inbreeding (F(IS) = 0.124-0.342) was observed in the embryo samples but not in three out of the four adult samples. The inbreeding level at the reproductive age was high only in the sample from Koryakia, which was explained by a relatively young age of plants in the population frequently affected by fires. A general increase in heterozygosity, characteristic of other conifers as well, was attributed to elimination of inbred progenies and by balancing selection for heterozygotes, which is a key factor maintaining allozyme polymorphism in populations.

Breeding↗
PubMed1980

[Population structure of forest Nentsee. II. Results of a geneologic study].

Inbreeding and its effect on fertility have been investigated in small (N approximately 1500) population of fisherman, hunters and reindeer breeders living in Northwestern Siberia. Average coefficient of inbreeding in total population was found to be 0.012, ranging from 0.003 to 0.016 between six subisolates. 8% of the total number of matings were matings between close relatives of uncle-niece, first cousins and double first cousins type. Nine polygamic matings were observed among presently living males belonging to elder generation. Comparative analysis of fertility in women whose reproduction had been completed was performed for 64 consanguineous and 120 non-consangineous matings. Insignificant decrease of average number of live births and surviving children was observed in matings of uncle-niece type and could be attributed to the greater number of sterile couples than in control matings. No differences have been observed when consanguineous matings of first cousins type were compared with control families with almost the same proportion of sterile couples. It can be concluded that if inbreeding has any distinct effect on fertility in families in the Forest Nentsee, this happens mainly as a result of increased proportion of sterile matings in inbred part of the population.

Consanguinity↗
PubMed1995

[Genetic-demographic study of mountain populations from Dagestan and their migrants to the lowlands. Comparison of basic parameters of fitness].

Results of a total genetic demography study of females of postreproductive age from both parts of "splits" highland isolates of Dagestan, highlanders, and migrants to lowlands are described. The components of natural selection that were related to differential mortality and differential fertility were estimated in the highlanders and the migrants using Crow indices. Offsprings of female migrants were characterized by a higher prenatal (spontaneous abortions and still-births) and a lower prereproductive mortality. These differences may be accounted for by two mechanisms: (1) the effects of changing marital structure (female migrants are more exogamous) and (2) better medical care for the children of migrants compared to those living in highland auls (settlements), which are still difficult to access. It was demonstrated that mortality of probands' children before reproductive age, as well as the proportion of their close genetic relatives that died within five years after resettling, increased with an increase in the level of individual inbreeding in women examined (probands). These data allow us to suggest that the drastic increase revealed in mortality of the highlanders during the first years after resettling may be partially attributed to high levels of inbreeding and heterozygosity; these, in turn, decrease the individual's nonspecific resistance to new ecological factors. Fertility and prenatal mortality appeared to increase and decrease, respectively, with an increase in the inbreeding level.

Adaptation, Physiological↗