The conflict between the Mendelian theory of particulate inheritance and the observation of continuous variation for most traits in nature was resolved in the early 1900s by the concept that quantitative traits can result from segregation of multiple genes, modified by environmental effects. Although pioneering experiments showed that linkage could occasionally be detected to such quantitative trait loci (QTLs), accurate and systematic mapping of QTLs has not been possible because the inheritance of an entire genome could not be studied with genetic markers. The use of restriction fragment length polymorphisms (RFLPs) has made such investigations possible, at least in principle. Here, we report the first use of a complete RFLP linkage map to resolve quantitative traits into discrete Mendelian factors, in an interspecific back-cross of tomato. Applying new analytical methods, we mapped at least six QTLs controlling fruit mass, four QTLs for the concentration of soluble solids and five QTLs for fruit pH. This approach is broadly applicable to the genetic dissection of quantitative inheritance of physiological, morphological and behavioural traits in any higher plant or animal.

Background Previous studies have reported additional cancers associated with BRCA mutations; however, type, magnitude of risk, and gender differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers. Methods An institutional review board approved study identified 1072 patients who had genetic counseling at our institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the general population cancer incidence rates. The expected and observed number of cases were calculated in 5 year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated. Results We identified 1177 cancers in the 1072 mutation carriers comprising 30 different cancer types. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had a significantly higher number of observed cases compared to expected cases for pancreatic cancer (SIR = 21.7, 95%CI = 13.1–34.0, p value <0.001) in both men and women and prostate cancer in men (SIR = 4.9, 95%CI = 2.0–10.1, p value =0.002). Conclusions The results of this study uphold the current recommendations for HBOC screening of cancers other than breast and ovarian by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings.

N RECENT YEARS, GENETIC TESTING for inherited cancer predisposition has become widely available. [1][2][3] Initially, the use of such testing was limited to those enrolled in research studies at specialized medical centers. However, developments in testing technology and widespread publicity in the news media have led to increased testing for conditions such as breast cancer susceptibility 4,5 in primary care [6][7][8] and other settings, raising questions about how to adequately inform patients about their personal breast cancer risk and the pros and cons of genetic testing. 9-11 Professional organizations advise that people who want to learn about their options and alternatives regarding genetic testing should be referred to specialists such as genetic counselors. 12-14 However, there are only about 400 genetic counselors in the United States who identify themselves as specializing in cancer genetics, 15 and cancer genetic counselors are not available in some regions of the Author Affiliations and Financial Disclosures are listed at the end of this article.

Little is known about how hereditary nonpolyposis colon cancer (HNPCC) genetic counseling and testing information is communicated within at-risk families. This article describes findings from a qualitative study of 39 adult members from five families with known HNPCC-predisposing mutations. We evaluated how information from HNPCC genetic counseling and testing was disseminated in these families and how family members reacted to and acted on this information. We included family members who had been diagnosed with an HNPCC syndrome cancer, unaffected individuals who were at 50% risk of carrying a mutation, and their spouses. Participants included those who had undergone testing and those who had not. In general, all families had shared the news about an HNPCC mutation with at-risk relatives. Communication about HNPCC genetic counseling and testing followed the norms used for conveying other nonurgent family news. Mutation noncarriers, nontesters, and those who were not biological relatives were less involved in discussing genetic counseling and testing and perceived these processes as less relevant to them. Although all family members were generally willing to share information about HNPCC, probands and mutation carriers informed extended family members and actively persuaded others to seek counseling or testing. Family members who were persuaded to seek those services by the proband were more likely to have counseling and testing and were more likely to seek those services sooner. Genetic counseling should attempt to identify the existing communication norms within families and ways that family members can take an active role in encouraging others to learn about their cancer risk and options for testing. Interventions may also need to emphasize the relevance of hereditary cancer information beyond the immediate family and to unaffected family members who may be central to the communication process (e.g., spouses of mutation carriers).