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Complex Inheritance (complex + inheritance)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Approaches to the identification of susceptibility genes

PARASITE IMMUNOLOGY, Issue 5 2009
A. COLLINS
SUMMARY Although previous studies have revealed a great deal about the genetic basis of susceptibility and resistance to parasite infection, there is now an opportunity to considerably enhance understanding through genome-wide association mapping. The application of association mapping to complex inheritance has recently become achievable given reduced costs, sophisticated genotyping platforms and powerful statistical methods which build upon increased knowledge of the linkage disequilibrium structure of the human genome. Linkage mapping and related approaches remain useful for the localization of the rarer genetic variants and candidate region association studies can be a very cost-effective route to progress. However, genome-wide association offers the greatest promise, despite the challenges posed by phenotype complexity, ensuring genotype coverage/quality and robust statistical analysis. The available approaches for mapping genes underlying susceptibility are reviewed here, emphasizing their relative merits and drawbacks and highlighting specific software tools and resources that enable successful mapping. [source]

Evidence for the multigenic inheritance of schizophrenia

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 8 2001
Robert Freedman
Abstract Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z,=,3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the ,7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z,=,2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci. © 2001 Wiley-Liss, Inc. [source]

Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1,

ANNALS OF NEUROLOGY, Issue 3 2009
Arvid Suls MSc
Absence epilepsies of childhood are heterogeneous with most cases following complex inheritance. Those cases with onset before 4 years of age represent a poorly studied subset. We screened 34 patients with early-onset absence epilepsy for mutations in SLC2A1, the gene encoding the GLUT1 glucose transporter. Mutations leading to reduced protein function were found in 12% (4/34) of patients. Two mutations arose de novo, and two were familial. These findings suggest GLUT1 deficiency underlies a significant proportion of early-onset absence epilepsy, which has both genetic counseling and treatment implications because the ketogenic diet is effective in GLUT1 deficiency. Ann Neurol 2009;66:415,419 [source]

A new endogenous retroviral sequence is expressed in skin of patients with psoriasis

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005
J-P. Molès
Summary Background, The origin of psoriasis, a chronic inflammatory skin disease involving keratinocyte proliferation, immune disturbances and complex inheritance, remains unknown. Human endogenous retroviruses (HERVs) are part of the normal human genome and their participation in the pathogenesis of various human diseases with complex genetic traits has been proposed. A possible role of HERVs in the induction of psoriasis was suggested many years ago. However, to date no study has searched for HERV expression in psoriasis. Objectives, To determine firstly, which HERV families are expressed in the psoriatic lesion and secondly, whether specific variants can be detected. Methods, HERV expression was analysed at the mRNA level after degenerated reverse transcription,polymerase chain reaction (RT,PCR) of retroviral pol sequences followed by sequencing. Screening for a specific variant was performed by RT,PCR on lesional and nonlesional psoriatic skin and compared with normal and atopic dermatitis skin. Results, We report the expression of three HERV families in psoriatic lesions, namely HERV-W, K and E. We then partially characterized a new endogenous retroviral variant, which was related to the ERV-9/HERV-W family. This sequence contains at least two open reading frames that could encode for a gag protein and a retroviral protease. The expression of this sequence was detected in 29 of 43 lesional psoriasis skin samples and rarely in normal (two of 21) or atopic dermatitis (three of 14) skin samples. Conclusions, In psoriatic lesions, HERV sequences of the W, K and E families are expressed and a new variant of the ERV-9/HERV-W family has been characterized. The possible role of HERV-related sequences in the pathogenesis of psoriasis is under investigation. [source]