GenePedigree

Why use it

A standardized pedigree makes inheritance patterns visible at a glance (autosomal dominant or recessive, X-linked, mitochondrial, multifactorial), identifies at-risk relatives for cascade testing, and is read the same way by every clinician and laboratory. Structured fields (ontology-coded conditions, HPO phenotypes, HGVS genotypes with ACMG classification) keep the clinical data exchangeable with risk models such as CanRisk/BOADICEA, with genealogy and linkage formats, and with electronic records through the GA4GH Pedigree FHIR model.

About

A pedigree is the standard graphical record of a family history: each person is a symbol, partnerships are horizontal lines, and descent lines connect parents to their children, generation by generation. GenePedigree draws pedigrees with the symbols of the Standardized Human Pedigree Nomenclature of the National Society of Genetic Counselors (NSGC), first published in 1995, updated in 2008 and revised in 2022 to separate sex assigned at birth from gender identity. In GenePedigree the symbol shape follows the sex assigned at birth (square, circle, or diamond) and is never redrawn for gender identity; when a different gender identity is recorded, the sex assigned at birth is written below the symbol (AFAB, AMAB, UAAB). Affected status is shown by shading, with quadrants for more than one condition; carriers by a central dot; presymptomatic individuals by a vertical line; deceased individuals by a diagonal line. Pregnancies, spontaneous abortions, terminations and stillbirths, adoption, twins, assisted reproduction (donor D, surrogate S), infertility and consanguinity each have their own notation. Generations are numbered with Roman numerals and individuals within a generation with Arabic numerals (for example II-3). Layout is automatic, using the layout algorithm of the Open Pedigree editor (PhenoTips), which handles consanguineous loops, multiple partnerships and twins without duplicating individuals. Consanguinity between partners is computed from the recorded relationships with Wright's coefficient of inbreeding, so that a union between relatives is detected even when it was not declared.

When to use

• Initial genetics or genetic counseling consultation: a three-generation family history of the proband or consultand
• Suspected hereditary cancer syndrome, before risk calculation in CanRisk/BOADICEA or another model
• Consanguineous families, to quantify the inbreeding coefficient of the offspring and recessive risk
• Prenatal and preconception counseling, including pregnancy losses, assisted reproduction and donors
• Planning cascade testing after a pathogenic variant is found in the family
• Exchanging a family history between services in PED, GEDCOM, CanRisk, FHIR, Invitae/Progeny XML or native JSON/YAML/XML

Method

Pearls & pitfalls

• Record at least three generations: first-, second- and third-degree relatives on both the maternal and paternal sides, including relatives who are unaffected.
• An arrow marks the consultand (the person seeking advice); an arrow with "P" marks the proband (the affected individual through whom the family comes to attention). They may be different people.
• Ask specifically about consanguinity, pregnancy losses, stillbirths, infertility, adoption and assisted reproduction: these are rarely volunteered and each changes the interpretation.
• The 2022 NSGC update separates sex assigned at birth from gender identity. Here the shape is kept by sex assigned at birth, so that relatives, laboratories and risk models read the drawing unambiguously; a recorded difference in gender identity is shown by AFAB, AMAB or UAAB below the symbol, and an organ inventory or karyotype is noted when relevant to risk.
• Offspring of first cousins have an inbreeding coefficient F = 1/16 (6.25% of loci homozygous by descent); uncle–niece unions F = 1/8; second cousins F = 1/64.
• In the 2008 nomenclature a central dot marks a carrier who is not expected to develop the condition, and a vertical line a presymptomatic carrier of a later-onset condition; the 2022 revision modified how carrier status is depicted, so a legend that states what each mark means keeps the drawing unambiguous.
• Adopted individuals are drawn in brackets; a dashed line connects an adopted-in child to the adoptive parents. Adoption does not create genetic relatedness.
• De-identify before sharing: remove names, exact dates and record numbers, keeping ages, which carry the clinical information.

Symbol key

• Male (assigned male at birth) — Square. The symbol shape follows the sex assigned at birth.
• Female (assigned female at birth) — Circle.
• Sex not known or intersex — Diamond: sex not specified, not known, or a difference of sex development.
• Gender identity differs from sex assigned at birth — The shape is unchanged; AFAB (assigned female at birth) or AMAB (assigned male at birth) is written below the symbol.
• Affected — Symbol filled; the condition is named in the legend.
• More than one condition — The symbol is divided into quadrants, one per condition, each shaded as in the legend.
• Suspected / possibly affected — Light shading of the symbol (or quadrant).
• Carrier (not expected to manifest) — Dot in the centre of the symbol.
• Presymptomatic carrier — Vertical line through the symbol: genetic result positive, clinically unaffected at present.
• Deceased — Diagonal line through the symbol; age at death written below when known.
• Stillbirth — Symbol with a diagonal line and "SB" with the gestational age below.
• Pregnancy — "P" inside the symbol, with gestational age or due date below.
• Spontaneous abortion (miscarriage) — Small triangle; "SAB" and gestational age below.
• Termination of pregnancy — Small triangle with a diagonal line; "TOP" and gestational age below.
• Proband — Arrow with "P": the affected individual through whom the family came to medical attention.
• Consultand — Arrow without "P": the person seeking counselling or testing.
• Adopted (in or out) — Brackets around the symbol; a dashed line of descent marks adoption into the family.
• Documented evaluation — Asterisk: the record was reviewed or the individual examined.
• Evaluated (test result) — "E" below the symbol; E+ positive and E− negative test result.
• Gamete donor — "D" inside the symbol (egg, sperm or embryo donor).
• Gestational carrier (surrogate) — "S" inside the symbol.
• Several individuals — A number inside the symbol: that many siblings of that sex, not drawn individually.

Lines

• Relationship line — Horizontal line joining partners; lines always meet each symbol at the middle of its side.
• Consanguineous relationship — Double relationship line. GenePedigree computes the kinship of the partners (Wright) and flags undeclared consanguinity.
• Separated or divorced — Relationship line crossed by short oblique strokes.
• Line of descent and sibship line — Vertical line from the relationship line to the horizontal sibship line, with one short vertical line to each child, in birth order from left to right.
• Monozygotic twins — Twin lines start from one point and are joined by a horizontal bar.
• Dizygotic twins — Twin lines start from one point, without a bar.
• Twins of unknown zygosity — Twin lines from one point with "?" below.
• No children by choice / infertility — Short vertical line ending in one bar (by choice or reason unknown) or two bars (infertility).
• Adopted into the family — Dashed line of descent to the adopted child (with brackets around the symbol).

Next steps

Confirm the reported diagnoses with records when they change management, and mark documented evaluations. Use the pedigree to choose the inheritance model, identify obligate carriers and at-risk relatives, and select the index case for testing. For hereditary breast and ovarian cancer, export to the CanRisk format to calculate risk. When a union between relatives is detected, declare the consanguinity and consider the higher prior probability of autosomal recessive conditions in the offspring. Review and update the pedigree at each visit, because family histories change.

Evidence

The NSGC nomenclature was proposed in 1995 by the Pedigree Standardization Task Force of the National Society of Genetic Counselors. The 2008 review of publications, journal instructions, professional societies and NSGC member comment found no significant objections or alternatives and described it as the only consistently acknowledged standard for drawing a family health history. The 2022 focused revision again found no fundamental alternative; it created no new symbols but clarified how sex assigned at birth and gender are recorded, and modified the depiction of carrier status. The level of evidence is expert consensus. Wright's coefficient of inbreeding (1922) is the standard measure of consanguinity in human and population genetics. The Open Pedigree layout algorithm comes from PhenoTips, a clinical phenotyping platform used in rare-disease programmes.

References

1. Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, et al. Recommendations for standardized human pedigree nomenclature. Pedigree Standardization Task Force of the National Society of Genetic Counselors. Am J Hum Genet. 1995;56(3):745-752. — link
2. Bennett RL, French KS, Resta RG, Doyle DL. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. J Genet Couns. 2008;17(5):424-433. — link
3. Bennett RL, French KS, Resta RG, Austin J. Practice resource-focused revision: Standardized pedigree nomenclature update centered on sex and gender inclusivity: A practice resource of the National Society of Genetic Counselors. J Genet Couns. 2022;31(6):1238-1248. — link
4. Wright S. Coefficients of inbreeding and relationship. Am Nat. 1922;56(645):330-338. — link
5. Girdea M, Dumitriu S, Fiume M, Bowdin S, Boycott KM, Chénier S, et al. PhenoTips: patient phenotyping software for clinical and research use. Hum Mutat. 2013;34(8):1057-1065. — link
6. Carver T, Hartley S, Lee A, Cunningham AP, Archer S, Babb de Villiers C, et al. CanRisk Tool—A web interface for the prediction of breast and ovarian cancer risk and the likelihood of carrying genetic pathogenic variants. Cancer Epidemiol Biomarkers Prev. 2021;30(3):469-473. — link
7. Carver T, Cunningham AP, Babb de Villiers C, Lee A, Hartley S, Tischkowitz M, et al. pedigreejs: a web-based graphical pedigree editor. Bioinformatics. 2018;34(6):1069-1071. — link
8. Global Alliance for Genomics and Health. GA4GH Pedigree FHIR Implementation Guide. — link