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A SNP-based genome-wide linkage scan is conducted to identify the various genes that lead to breast cancer in families with cases not associated with BRCA1 or BRCA2 germline mutations. The phenotypic and geographic homogeneity are considered to be the most important factors that need to be considered while performing such studies.

Nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) are representative of complex genetic traits. Disease loci of CP/P and CPO can be hypothesized to be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting have been screened for LD with either CL/P or CPO in a population mainly Caucasian. Both case-control- and nuclear-family-based approaches were used. No common mutations were found in the coding regions in a mutation search in certain genes in 69 CPO patients and in a group within the larger group of CL/P patients. Several rare variants of MSX1 and TGFB3 were found. Results are a foundation for further research.

The locus of the inherited renal carcinoma (RC) mutation was mapped to rat chromosomal band near the protamine locus, using linkage studies, which reveal tumors loss homology at this locus indicating that this putative tumor suppressor gene is recessive. The human homology of the RC gene could be present on human chromosome 16, not believed to be changed ordinarily in human RC. In the rat, a type of primarily inherited RC causes multiple chromophobe cell tumors, similar to the human disease, and heterozygous carriers are very vulnerable to radiation and chemical carcinogens.

In Laron dwarfism (LD), a genetic disease, the body does not respond to growth hormone (GH), despite an increase in GH secretion. Because GH interacts with growth hormone receptor (GH-receptor), it is thought that there may be a defect of, or deficiency in, this cell receptor in individuals with LD. To explore the question of whether there could be a defect in the gene that is responsible for GH-receptor, genetic material from individuals with LD and their families was evaluated. The study group included two Mediterranean families in which the parents were blood relatives and some of the children had LD. The results revealed that the genetic trait for LD and genetic abnormalities of LD were always inherited together. Using genetic linkage techniques, a specific DNA mutation was identified in these families. This mutation caused a defect in a protein that is involved in the development of GH-receptor. Seven unrelated individuals with LD were also studied; the mutation found in the families did not occur in these individuals. Further analysis of the genetic material of the seven individuals indicated that different mutations were responsible for these cases of LD. It is suggested that LD can be caused by a genetic mutation that occurs independently in each family, and that this mutation can vary from family to family. More genetic studies of LD families will be necessary to locate other mutation sites responsible for this syndrome. (Consumer Summary produced by Reliance Medical Information, Inc.)