Pedigrees
المؤلف:
Cohn, R. D., Scherer, S. W., & Hamosh, A.
المصدر:
Thompson & Thompson Genetics and Genomics in Medicine
الجزء والصفحة:
9th E, P111-112
2025-12-11
43
Single-gene disorders are characterized by their patterns of transmission in families. A usual first step is to obtain information about the patient’s family history and to summarize the details in the form of a pedigree – a graphical representation of the family tree – with use of standard symbols (Fig. 1). Some of these symbols and drawing styles are strongly established, such as the use of a square symbol for a male and a circle for a female. Others vary among users and evolve to accommodate changing needs (e.g., to differentiate sex from gender or to accommodate assisted reproduction options). How to differentiate phenotype and genotype can be a point for consideration, especially as sequence information becomes more prevalent. Many professionals advocate the need for standardization, particularly as computer generated pedigree drawings become more widespread, but there is not yet one established authority. Drawings in this text reflect a variety of current styles of presenting such pedigrees. The most important considerations are to be clear and practical and to define the symbols and abbreviations used for the drawing.
Fig1. Symbols used in pedigree charts. Although there is no uniform system of pedigree notation, the symbols used here are commonly used by professionals in the field of genetic counseling. 1Modifiers below symbol: AMAB (assigned male at birth), AFAB (assigned female at birth), UAAB (unassigned at birth), no notation = unknown or not specified 2LMP = last menstrual period (date) 3Note that this symbol may be inappropriate when multiple genotypes are involved (Practice Resource Focused Revision: Standardized pedigree nomenclature update centered on sex and gender inclusivity: A practice resource of the National Society of Genetic Counselors Robin L. Bennett et al.) J Genet Couns. 2022;00:1–11.
The extended family depicted in such pedigrees is a kindred (Fig.2). An affected individual through whom a family is first brought to medical attention (i.e., is ascertained) is the proband, propositus, or index case. The person who consults a health professional is referred to as the consultand (or perhaps patient or client) who may or may not themself be affected. Probands and consultands are sometimes differentiated on the pedigree with P or C beside their respective arrows. A family may have more than one proband if they are ascertained through more than one source. Brothers and sisters are called sibs or siblings, and a family of sibs forms a sibship. Relatives are classified as first degree (parents, sibs, and offspring), second degree (grandparents and grandchildren, uncles and aunts, nephews and nieces, and half-sibs), or third degree (e.g., first cousins), and so forth, depending on the number of steps in the pedigree between the two relatives. Couples who have one or more ancestors in common are consanguineous. If the proband is the only affected member in a family, that person is an isolated (or sometimes sporadic) case. When there is a definitive diagnosis based on comparisons to other patients, well established patterns of inheritance in other families with the same disorder can often be used as a basis for counseling, even with an isolated case.
Fig2. Relationships within a kindred. Generations are designated with roman numerals; individuals within each generation are specified by arabic numerals above the symbols. The proband, III-5(arrow), represents an isolated case of a genetic disorder. She has four siblings: III-3, III-4, III-7, and III-8. Her partner/spouse is III-6, and they have three children (their F1 progeny). The proband has nine first-degree (1°) relatives (her parents, siblings, and offspring), nine second-degree (2°) relatives (grandparents, uncles and aunts, nieces and nephews, and grandchildren), two third-degree (3°) relatives (first cousins), and four fourth-degree (4°) relatives (first cousins once removed). IV-3, IV-5, and IV-6 are second cousins of IV-1 and IV-2. IV-7 and IV-8, whose parents are consanguineous, are doubly related to the proband: second-degree relatives through their father and fourth-degree relatives through their mother.
Examining a pedigree is an essential first step in determining the inheritance pattern of a genetic disorder in a family. There are, however, situations that may make this difficult to discern in an individual pedigree. For example, in a family with a lethal disorder affecting a fetus early in pregnancy, one may observe only multiple miscarriages or reduced fertility. For phenotypes with delayed onset, a family may include members who have not yet reached the age at which the disease reveals itself. Nonpenetrance or variable expressivity may make it difficult to obtain accurate information about the existence of relatives carrying a pathogenic genotype. Family relationships may be inaccurately described. Finally, in smaller families, the proband may happen to be the only affected family member, making determination of any inheritance pattern very difficult.
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