Pedigree Analysis of Genetic Marker co-occurence

The pedigree in (A) shows the co-occurence of a disease through three generations with genetic variation at locus M found in a mother. The occurence of the disease in three generations suggests autosomal dominant inheritance: only one allele is required to produce the condition, and the condition is equally frequent in males and females. Genotyping of the mother shows she is heterozygous for two alleles (M1/M2).

The analysis in (B) tests two alternative hypothesis, that either allele M1 or M2 is genetically linked to the disease state (Hypothesis 1 and 2, respectively). Because all three offspring with M1 are affected, and two of three children with M2 are unaffected while the third is affected, Hypothesis 1 can explain the distribution by invoking only a single recombination event that un-links the M1 markers from the disease state; Hypothesis 2 requires five such events

Reconstruction of the maternal grandmother's genotype (C) then implies that she also had allele M1, which would explain her disease state. It may be possible to determine her actual genotype, for example by genetic analysis of tissue on decades-old biopsy slides. This information may be useful in predicting occurence of the disease in other family members)
and .

Figure 2012 TA Brown, Introduction to Genetics (1st ed.); additional text 2013 by Steven M. Carr