医学遗传学基础第七次课-atypical mendelian inheritance.pptx

Atypical Mendelian Inheritance;Anticipation in myotonic dystrophy. Number of CTG repeats is indicated below each symbol. Each individual has one normal allele of 5 repeats. In the first generation, the affected individual has a 65 repeat allele that gives rise to mild myotonic dystrophy. This increases to 95 repeats in his affected son, then to 200 repeats in his affected daughter, and finally to 700 repeats in severely affected child in the last generation. ;Pseudodominant inheritance in hemochromatosis(Carrier freq is as high as 1/10 in individuals of Celtic ancestry). A heterozygous male and homozygous female transmit a recessive disorder to their daughter, giving the appearance of dominant transmission. This is most likely to occur when the mutant allele is common in the population. ;X-linked dominant inheritance with male lethality. Pedigree illustrating X-linked dominant transmission. Only females are affected. Males who inherit the mutant allele a die in utero.;Pedigree of a pseudoautosomal condition. The allele causing this dominant condition is on the Y chromosome in affected males marked Y, but on the X chromosome in all other affected individuals. The three individuals marked with a red asterisk are the result of an X-Y crossover in their father. Note how the pedigree is indistinguishable from an autosomal dominant pedigree, although the causative gene is located on Xp or Yp.;The mother of the two affected children is a mosaic for the mutation. She does not show signs of the disorder, or signs may be exceptionally mild or limited to a restricted region of the body. If she is a germline mosaic, only egg cells would carry the mutation. ;Imprinting. Pedigree of family with hereditary paragangliomas, in which the mutant gene is only expressed if inherited from the father. Examples of apparent nonpenetrance are due to inheritance of the mutation from a female.;Digenic inheritance. Individual I-1 is heterozygous for a mutation in gene A (A-) and I-2 is heterozy