The Continuing Evolution Of The Pedigree In The Age Of Genomic Medicine

Thanks to the International Human Genome Project, the genes of the human genome are likely to be located and sequenced by the year 2003. The ability to practice genomic medicine, by potentially viewing the molecular status of each patient's individual genome, has an impact on all medical disciplines. Yet it is absurd to think

THE CONTINUING EVOLUTION OF THE PEDIGREE IN THE AGE OF GENOMIC MEDICINE 11

TABLE 1.2 Common Patient Misconceptions about Inheritance

0 If no one else in the family is affected, the condition is not inherited.

0 If several people in the family have the same condition, it must be inherited.

0 All birth defects are inherited.

0 The parents (particularly the mother) must have done something before conception or during the pregnancy to "cause" the condition in their fetus or child.

0 With a 25% recurrence risk, after one affected child, the next three will be unaffected.

0 With a 50% recurrence risk, every other child is affected.

0 Birth order influences disease status (for example, only the eldest or youngest child can be affected).

0 If the affected individuals in the family are all women, or all men, the condition must be sex-linked.

0 A person will inherit the genetic condition because he or she "looks" or "acts" like the affected relative(s). Or the opposite—a person will not inherit a condition because he or she bears no resemblance to the affected relative(s).

0 For a condition with sex-influenced expression (such as breast cancer), individuals of the opposite sex cannot transmit the condition (for example, a male cannot pass on a gene alteration for breast cancer).

Source: Revised from Connor and Ferguson-Smith, 1997.

that a complete genomic reference map will then lead us to the understanding of all that is human or that we are the direct and inevitable consequence of our genome. The genetic family history will continue to play an essential role in the medicine of the 21st century. As Dr. Reed Pyeritz (1997), President of the American College of Medical Genetics, succinctly summarizes:

The importance of the family history will only be enhanced in the future. Even when an individual's genome can be displayed on a personal microchip, interpreting that information will depend in large part, on the biological and environmental contexts in which the genome is expressed, and the family milieu is as good a guide as any. Physicians can help define those contexts through careful family and social histories. How those histories can be obtained and interpreted, when the average time for patient interaction with a physician continues to diminish, are crucial areas for research.

Variation is the hallmark of humans—even within well-established diseases with known patterns of inheritance, there is remarkable disease variability. Pedigree assessment will continue to play a critical role in our understanding of gene expression. A patient who has a genetic disorder, or one who carries a genetic susceptibility mutation, cannot be viewed in isolation from the background of his or her family history. How is it that five relatives with the same gene mutation can all have different ages of onset and varying manifestations of the same genetic disorder? The patient and his or her genotype must be examined in the context of his or her genetic and environmental exposures. The clues from buried ancestors can reach out to the present to provide solutions for the future.

REFERENCES

American College of Obstetricians and Gynecologists (1987). Antenatal diagnosis of genetic disorders (ACOG Technical Bulletin 108). Washington DC: ACOG.

American College of Obstetricians and Gynecologists (1998), Stone ML (ed). Screening and early detection of gynecologic malignancies (ACOG Update Vol 23). Washington DC: ACOG.

American Society of Clinical Oncologists (1997). Resource document for curriculum development in cancer genetics education. J Clin Oncol 15:2157-2169.

Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan C (1993). The need for developing standardized family pedigree nomenclature. J Genet Couns 2:261-273.

Bennett RL, Steinhaus KA, Uhrich SB, et al. (1995). Recommendations for standardized human pedigree nomenclature. Am J Hum Genet 56(3):745-752.

Burke W, Daly M, Garber J, et al. (1997a). Recommendations for follow-up care of individuals with an inherited predisposition to cancer II. BRCA1 and BRCA2. JAMA 227:997-1003.

Burke W, Petersen G, Lynch P, et al. (1997b) Recommendations for follow-up care of individuals with an inherited predisposition to cancer I. Hereditary nonpolyposis colon cancer. JAMA 277(11):915-919.

Childs B (1982). Genetics in the medical curriculum. Am J Med Genet 13:319-324.

Connor M, Ferguson-Smith M (1997). Essential Medical Genetics, 5th ed. Oxford: Blackwell Science.

Galton F (1889). Natural Inheritance. London: MacMillan.

Huson SM, Rosser, EM (1997). The phakomatoses. In Rimoin DL, Connor JM, Pyeritz RE (eds), Emery and Rimoin's Principles and Practice of Medical Genetics, 3rd ed. New York: Churchill Livingstone, pp. 2269-2302.

Linehan WM, Klausner RD (1998). Renal carcinoma. In Vogelstein B, Kinzler KW (eds), The Genetic Basis of Human Cancer. New York: McGraw Hill, pp. 455-473.

Mazumdar PMH (1992). Eugenics, Human Genetics and Human Failings. London, New York: Routledge.

Online Mendelian Inheritance in Man, OMIM (TM). Center for Medical Genetics, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 1997. Accessed June 19, 1998. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/

Pyeritz RE (1997). Family history and genetic risk factors. Forward to the future. JAMA 278 (15):1284-1285.

Resta RG (1993). The crane's foot: The rise of the pedigree in human genetics. J Genet Couns 2(4):235-260.

Resta RG (1995). Whispered hints. Am J Med Genet 59:131-133.

Steinhaus KA, Bennett RL, Uhrich SB, et al. (1995). Inconsistencies in pedigree nomenclature in human genetics publications: a need for standardization. Am J Med Genet 56(5):291-295.

The Practical Guide to the Genetic Family History. Robin L. Bennett

Copyright © 1999 Wiley-Liss, Inc. ISBNs: 0-471-25154-2 (Paper); 0-471-22391-3 (Electronic)

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