Disease Loci

Department of Integrative Biology, University of California, Berkeley, California, U.S.A. 

In contrast to Mendelian diseases, complex, or multifactorial diseases, are generally more common, and result from the interaction of multiple genes and environmental factors. Studies of rates of occurrence of disease in twins and other family members compared to population level rates are used to demonstrate the role of genetic and environmental factors in complex diseases (3,4). 

Genetically complex diseases may exhibit the following properties incomplete penetrance—not all susceptible individuals are affected the 

Markers such as protein and blood group loci were initially used in the analysis of genetic traits however they were limited in utility due to low variation. Early in the 1980s these markers began to be replaced with DNA polymorphisms, initially RFLPs which are detected by the ability of a segment of DNA to be cut, or to not be cut, by a specific restriction enzyme. 

The LD can occur in populations as a consequence of a number of factors (see Ref. 13 for review) mutation when a new mutant arises, it occurs in one individual and is in LD with all polymorphic loci in the population selection—either acting directly on the two loci, or transient LD can also be created with neutral loci via a hitchhiking event with a selected locus (14) migration or admixture—generation of LD by these forces requires that the allelic frequencies of both loci in the two populations be different, and this difference must be substantial to generate very much LD and random genetic drift—while the expected value of pairwise LD due to drift over 

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APOE is the only established late-onset Alzheimer s disease gene 656 Other late-onset Alzheimer s disease loci 656... 

Early-onset familial Parkinson s disease 657 Parkin accounts for the majority of early-onset Parkinsonism 658 DJI and PINK1 are recessively acting Parkinson s disease genes 658 Other proposed early-onset Parkinson s disease loci 658 Late-onset Parkinson s disease 658... 

Other proposed early-onset Parkinson s disease loci. In... 

T. Nenguke, M. I. Aladjem, J. F. Gusella, N. S. Wexler, and N. Arnheim, Candidate DNA replication initiation regions at human trinucleotide repeat disease loci. Hum. Mol. Genet. 12, 1021-1028 (2003). 

Barcellos LF, Klitz W, Field LL, Tobias R, Bowcock AM, Wilson R, Nelson MP, Nagatomi J, Thomson G. Association mapping of disease loci, by use of a pooled DNA genomic screen. Am J Hum Genet 1997 61 734—747. 

Carlson CS, Eberle MA, Kruglyak L, Nickerson DA. Mapping complex disease loci in whole-genome association studies. Nature 429 446 -52. 

Trembath RC, Clough RL, Rosbotham JL, et al. Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet 1997 6 813-820. 

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