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At least 451 records · Page 25Linked to original sources
PubMed2000

A frailty model of segregation analysis: understanding the familial transmission of alcoholism.

Coupled with environmental factors, genes contribute to numerous human diseases and traits. While there are many epidemiological methods to assess the familial clustering of traits, few are flexible enough to accommodate interactions between covariates and familial factors. In this paper, we propose and develop a frailty model that establishes an integrated framework to evaluate familial transmission of a disease by controlling for covariate effects and conveniently testing the interactions between covariates and familial factors. We also present a peeling algorithm that dramatically reduces the computational burden. This frailty model is employed to examine the familial transmission of major subtypes of alcoholism, namely, alcohol abuse and dependence. We conclude that alcohol dependence is strongly familial whereas alcohol abuse expresses a marginally significant pattern of familial transmission. Moreover, females manifest alcoholism at a lower threshold, and there is no sex-specific familial transmission of alcoholism after adjustment for the threshold effect.

Alcoholism↗
PubMed1987

Choroideremia: close linkage to DXYS1 and DXYS12 demonstrated by segregation analysis and historical-genealogical evidence.

Linkage studies using restriction fragment length polymorphisms were conducted in the X-linked disorder, choroideremia, designated TCD for Progressive Tapeto-Choroidal Dystrophy. Previously demonstrated close linkage with locus DXYS1 was confirmed (lod 11.44 at 0 recombination distance). In addition, locus DXYS12 was found to be closely linked with TCD (lod 3.31 at 0 recombination distance). The disease mainly occurs in three large kindreds in remote Northern Finland. While formal genealogical proof is lacking, all presently living (more than 80 affected males and 120 carrier females) probably originate from a common founder couple born in 1644 and 1646, twelve generations ago. All 36 patients and 48 carriers tested from the three kindreds had the same haplotype (TCD/DXYS1, 11kb/DXYS12, 1.6kb). Given that at least 105 female meioses transmitting TCD have occurred since 1650 in these kindreds, extremely close linkage between TCD, DXYS1 and DXYS12 is suggested. The above haplotype is a very useful diagnostic tool in these TCD families. We suggest that our historical-genealogical approach to linkage analysis may be possible elsewhere in similar isolated populations.

Alleles↗
PubMed1996

A three-allelic polymorphic system in exon 12 of the LDL receptor gene is highly informative for segregation analysis of familial hypercholesterolemia in the Spanish population.

We have screened exon 12 of the low density lipoprotein (LDL) receptor gene from 46 familial hypercholesterolemia (FH) heterozygotes and 64 normolipidemic controls for two polymorphisms, HincII, which is caused by a T to C substitution at base 1773, and a C to T transition at base 1725, by using single strand conformation polymorphism (SSCP) analysis. Our results indicate that polymorphism at base 1725, previously reported as very rare from a Japanese sample, is quite frequent in the Spanish population and that it is closely linked to the presence of the HincII site (HincII+). Thus, both polymorphisms constitute a system of three alleles, typed HincII- C1725, HincII+ C1725, and HincII+ T1725, whose frequencies in the FH sample were 0.489, 0.347, and 0.164, respectively. No significant differences were found in the allele frequencies between the FH and control samples. This three-allelic polymorphic system provides a higher information content (PIC value) than the HincII RFLP alone (0.537 versus 0.373, respectively); therefore, it is an extremely useful marker for linkage analysis of FH in Caucasian populations.

Deoxyribonucleases, Type II Site-Specific↗
PubMed1984

An epidemiological and genetic study of facial clefting in France. II Segregation analysis.

Familial transmission of cleft lip with or without cleft palate (CL(P] and isolated cleft palate (CP) was studied in two French samples of 458 CL(P) and 156 CP nuclear families, using the recently implemented unified model. In neither case could discrimination be achieved between polygenic inheritance and monogenic inheritance with a high proportion of sporadic cases. In this type of disorder with a complex genetic basis the information furnished by such an approach, which only considers the affected status, is discussed. Future investigations on the joint familial transmission of the disease and different marker systems may help to identify the genes involved in these developmental anomalies.

Cleft Lip↗
PubMed1990

Segregation analysis of peripheral neurofibromatosis (NF1).

Four studies of NF1 support a prevalence of 0.0003 and a carrier incidence at birth of 0.0004. The gene frequency (q) is therefore 0.0002, and the proportion of cases owing to fresh mutation is 0.56. The mutation rate (xq) is 10(-4), an unusually high value suggestive of a large gene. Penetrance among subjects examined is virtually complete, and there is no evidence of phenocopies or somatic mutations.

Child↗
PubMed1992

Segregation analysis reveals tight genetic linkage between the spontaneously arising neural tube defect gene splotch (Sp) and Pax-3 in an intraspecific mouse backcross.

Concurrent research has recently characterized Sp2H, a radiation induced mutation at the splotch (Sp) locus, and found alterations in the murine paired box gene, Pax-3, in homozygous Sp2H DNA. It was proposed that Sp and Pax-3 are the same gene. This report presents additional genetic evidence in support of this finding through linkage studies. Southern blot analysis of genomic DNAs from a panel of 125 intraspecific [(Sp/+ x CBA/J)F1-Sp x CBA/J] backcross mice reveals no crossover between Pax-3 and the spontaneously occurring splotch allele, Sp. This positions Pax-3 within 2.9 cM of the Sp locus (95% confidence interval) and suggests tight genetic linkage between the two marker genes.

Animals↗