Offspring Of First Cousin Marriage Research Articles

Consanguinity and congenital anomalies

Journal of Paediatrics and Child HealthVolume 50, Issue 3 p. 243-243 Heads UpFree Access Consanguinity and congenital anomalies First published: 27 March 2014 https://doi.org/10.1111/jpc.12527_4Citations: 3AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Medical staff is often consciously or unconsciously judgmental about consanguineous couples who give birth to babies with congenital anomalies. The Born in Bradford study is a prospective birth cohort study of 13 776 babies born between 2007 and 2011 in Bradford, North England.1 Questionnaire data were available for 11 396 babies (82.7%), of whom 386 (3%) had a congenital anomaly. The rate in Bradford (30.6 per 1000 live births) was higher than the nationally reported rate (17.0 per 1000). The risk of congenital anomaly was twice as high in Pakistani mothers as in ‘white British’ mothers (RR = 1.96, 95% CI 1.56–2.46), and this was largely attributable to consanguinity. The 18% of babies who were the offspring of first cousin marriages had slightly over twice the risk of congenital anomaly (RR = 2.19, 95% CI 1.67–2.85). This increased risk was similar to that of older white British mothers >34 years old (RR = 1.83, 95% CI 1.14–3.00). There was no association of congenital anomaly with poverty, but maternal education to degree level halved the risk (RR = 0.53, 95% CI 0.38–0.75). These data help quantify the size of the increased risk of congenital anomaly associated with consanguinity. Reference 1 Sheridan E et al. Lancet 2013; 382: 1350– 1359. CrossrefPubMedWeb of Science®Google Scholar Reviewer: David Isaacs, david.isaacs@health.nsw.gov.au Citing Literature Volume50, Issue3March 2014Pages 243-243 ReferencesRelatedInformation

Consanguinity and Prereproductive Mortality in the Utah Mormon Population

To test the effects of parental consanguinity on mortality among offspring, inbreeding coefficients were estimated for 303,675 members of the Utah Mormon population who were born between 1847 and 1945. Although consanguinity has been relatively rare in this population, the large sample size permitted the identification of more than 3,500 inbred offspring. Among the offspring of unrelated parents, 13.2% died before the age of 16. Significant elevations in prereproductive mortality were seen among the offspring of first-cousin marriages (22%) and among the offspring of closer unions (32%). The cor- responding relative risks are 1.70 (95% confidence limits = 1.52, 1.91) and 2.41 (95% confidence limits = 1.59, 3.41), respectively. Other categories of relationship did not produce significant elevations in offspring mortality. Similar results were obtained when a case-control approach was used to remove the effects of socioeconomic variation. Consistent with many other studies of populations with low consanguinity rates, this population experienced a relatively high absolute increase in mortality among the offspring of first-cousin marriages (9%). Preliminary evidence is offered for the hypothesis that mortality differentials are larger in populations with low inbreeding and low mortality because nongenetic causes of death do not obscure the effects of consanguinity.

Linkage of combined factors V and VIII deficiency to chromosome 18q by homozygosity mapping.

Combined Factors V and VIII deficiency is an autosomal recessive bleeding disorder identified in at least 58 families comprising a number of different ethnic groups. Affected patients present with a moderate bleeding tendency and have Factor V and Factor VIII levels in the range of 5-30% of normal. The highest frequency of the mutant gene is found in Jews of Sephardic and Middle Eastern origin living in Israel with an estimated disease frequency of 1:100,000. We sought to identify the gene responsible for combined Factors V and VIII deficiency using a positional cloning approach. Of 14 affected individuals from 8 unrelated Jewish families, 12 were the offspring of first-cousin marriages. After a genome-wide search using 241 highly polymorphic short tandem repeat (STR) markers, 13 of the 14 affected patients were homozygous for two closely linked 18q markers. Patients and all available family members were genotyped for 11 additional STRs spanning approximately 11 cM on the long arm of chromosome 18. Multipoint linkage analysis yielded a maximal log of the odds (LOD) score of 13.22. Haplotype analysis identified a number of recombinant individuals and established a minimum candidate interval of 2.5 cM for the gene responsible for combined Factors V and VIII deficiency. The product of this locus is likely to operate at a common step in the biosynthetic pathway for these two functionally and structurally homologous coagulation proteins. Identification of this gene should provide new insight into the biology of Factor V and Factor VIII production.

Biosocial perspective of consanguineous marriages in rural and urban Swat, Pakistan.

Consanguineous marriages in two population samples, one rural and one urban, from Swat (Pakistan) were studied. The frequency of consanguineous marriages was found to be 37.13% and 31.11%, and mean inbreeding coefficients were calculated as 0.0168 and 0.0162, for the rural and urban populations respectively. The most frequent type of marriage was between first cousins, in both samples. Among first cousin marriages, those with father's brother's daughter were predominant. Mean inbreeding coefficient was higher for higher socioeconomic groups in both samples. Differences by ethnic and educational groups were also found. Contrary to previous studies, a significant increase in the incidence of consanguineous marriages over the years has been observed. The incidence of premature mortality was significantly higher only in the offspring of first cousin marriages. Significantly higher incidence of morbidity in the offspring of consanguineous marriages was also observed.

HLA-Dw clusters associated with DR4 in Israeli Jews and the definition of a new DR4 associated Dw subtype: Dw“SHA”

A homozygous typing cell (HTC), that identifies a newly defined HLA-Dw determinant Dw“SHA”, is described. The donor of the HTC was a Yeminite Jew and an offspring of first cousin marriage. This cell is not included in the known DR4-associated specificity clusters Dw4,Dw10,Dw13,Dw14,Dw15, or the provisional cluster Dw“KT2”. Dw“SHA” was shown to segregate with DR4 positive haplotypes in family analysis, and in a population study was present in three of 43 unrelated DR4 positive individuals. This new Dw determinant was detected in Israeli Jews of Yemenite origin bearing the haplotype HLA-Bw41,DR4,DQw3. This indicates that Bw41,DR4,DQw3,Dw“SHA” may represent a typical allele combination in Yemenite Jews. Among 43 DR4 haplotypes in Israeli Jews, Dw10 had the highest antigen frequency (41.8%), whereas in American Caucasoids and in Japanese, Dw4 and Dw15 were most frequent, 44% and 40.5%, respectively.

An epidemiologic approach to the evaluation of the effect of inbreeding on prereproductive mortality.

Although many studies report deleterious effects of inbreeding on prereproductive mortality (death before age 20 years), such effects are usually measured in terms of genetic load, a concept much debated in the literature. To evaluate the public health impact of inbreeding on prereproductive mortality in terms of relative and attributable risks, the authors reviewed 31 studies with 294 observations comparing various stages of infant and child mortality in offspring of unrelated parents with offspring of first cousin, first cousin once removed, and second cousin marriages, respectively. Compared with offspring of unrelated parents, offspring of first cousin marriages have a higher risk of prereproductive mortality (median relative risk (RR) = 1.41, signed-rank test, p less than 0.01). Offspring of first cousin once removed and second cousin marriages had median relative risks of 1.16 and 1.26, respectively. Countries with relatively higher rates of consanguineous marriages (greater than 5%) had lower median relative risks than did countries with lower consanguinity rates. Also, the higher the mortality rate in the population, the lower the effect of consanguinity (median relative risk). Because of the rarity (less than 5%) and declining trends of consanguineous marriages in many places of the world, and because of their modest effect on prereproductive mortality (RR less than 2.0), it can be shown that the attributable risk of prereproductive mortality due to consanguineous marriages is less than 5%. Except for a few places with very high inbreeding levels, inbreeding has a minor impact on mortality in the prereproductive period.

Effects of inbreeding on cognitive performance.

THE few studies1,2 in which the effects of inbreeding on cognitive performance have been examined revealed that offspring of first-cousin marriages had lower IQ scores than offspring of unrelated parents. These studies were, however, performed in societies where the population engaging in such marriages is a small (1%, 6%)2,3 and unrepresentative proportion of the total population. Possible confounding of the effects of inbreeding with the effects of other intelligence-related variables such as socioeconomic status may lead the effects of inbreeding to be overestimated2. Unfortunately statistical control may either over- or under-correct for the correlates of the independent variables, leaving one in doubt about the true effect of inbreeding. I have now examined the effects of inbreeding on cognitive performance in an Arab population with a high rate of consanguinous marriage which minimised the distortions due to non-genetic variables. I show here that offspring of unrelated parents performed better than offspring of first-cousin marriages in intelligence and achievement tests administered at grades 4 and 6. The lowest level of performance and a higher variance were found for offspring of double-cousin marriages. The inbreeding depression found in this study is consistent and cannot be explained by the effects of socioeconomic status. I drew a nationally representative sample of 3,203 children in grades four and six (approximate ages 10 and 12 yr) of the Arab educational system in Israel. This sample constitutes about 10% of the total population in these grades and includes only normal (not retarded) children. Column 1 in Table 1 shows the division of the subjects according to grade level and consanguinity of the parents. A first-cousin marriage is between children of siblings. Children of first cousins have, on average, 1/16 pairs of genes by common descent. Double first cousins are children of siblings married to unrelated siblings. When they marry, their children have, on the average, 2/16 pairs of genes by common descent.

Why is the XX fitter? Evidence consistent with an effect of X-heterosis in the human female from sex ratio data in offspring of first cousin marriages.

Why is the XX Fitter? Evidence Consistent with an Effect of X-heterosis in the Human Female from Sex Ratio Data in Offspring of First Cousin Marriages

Letter: Why is the XX fitter? Evidence consistent with an effect of X-heterosis in women from sex ratio data in offspring of first cousin marriages.

Letter: Why is the XX fitter? Evidence consistent with an effect of X-heterosis in women from sex ratio data in offspring of first cousin marriages.