A SImplified method for Segregation Analysis (SISA) to determine penetrance and expression of a genetic variant in a family.
Hum Mutat
; 32(5): 568-71, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-21309035
ABSTRACT
A method for SImplified rapid Segregation Analysis (SISA) to assess penetrance and expression of genetic variants in pedigrees of any complexity is presented. For this purpose the probability for recombination between the variant and the gene is zero. An assumption is that the variant of undetermined significance (VUS) is introduced into the family once only. If so, all family members in between two members demonstrated to carry a VUS, are obligate carriers. Probabilities for cosegregation of disease and VUS by chance, penetrance, and expression, may be calculated. SISA return values do not include person identifiers and need no explicit informed consent. There will be no ethical complications in submitting SISA return values to central databases. Values for several families may be combined. Values for a family may be updated by the contributor. SISA is used to consider penetrance whenever sequencing demonstrates a VUS in the known cancer-predisposing genes. Any family structure at hand in a genetic clinic may be used. One may include an extended lineage in a family through demonstrating the same VUS in a distant relative, and thereby identifying all obligate carriers in between. Such extension is a way to escape the selection biases through expanding the families outside the clusters used to select the families.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Variación Genética
/
Penetrancia
/
Predisposición Genética a la Enfermedad
/
Modelos Teóricos
Límite:
Humans
Idioma:
En
Revista:
Hum Mutat
Asunto de la revista:
GENETICA MEDICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Noruega