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Segregation and patterns of
human inheritance
Material covered in this lecture is partly
review; however we will cover exceptions to
standard patterns of inheritance more
completely than is usually done in an
introductory course.
It is assumed that each student is familiar
with the terminology on pp. 51-52 and with
the analysis of pedigrees, Figs. 5-1 (p. 52), 52 (p. 53) and handouts.
Dominance vs Recessiveness
Refers to phenotype
– however, common to use in reference to
– can be ambiguous! HbS (recessive sickle
cell anemia, co-dominant expression of
globin, dominant malaria resistance)
Incomplete dominance
– phenotype of homozygote more severe
than that of heterozygote
– both phenotypes expressed
Dominant phenotypes - why
isn’t one good copy of a gene
Dominant negative effects
Gain of function mutations
Inherited susceptibility: inheritance of
one mutant allele with subsequent loss
of heterozygosity as a somatic mutation
Autosomal recessive
Autosomal recessive phenotype
typically see in sibship of proband but
not in parents or offspring or other
Males and females equally affected
Parents of affected individual often
Recurrence risk for each sib of proband
= 1 in 4 (25%)
Autosomal dominant
Phenotype usually appears in each
generation (except when new mutation
or incompletely penetrant)
Any child of affected parent has 50%
chance of inheriting the trait
Phenotypically normal individuals do not
normally transmit the trait
Males and females equally affected and
equally likely to transmit
Many cases due to new mutation
X-linked recessive inheritance
Incidence of trait higher in males than in
Heterozygous females usually
unaffected but may manifest with
variable severity due to XCI
Responsible allele passed from male to
all daughters and from heterozygous
female to 50% of her sons
A significant number of cases are due to
new mutation
X-linked dominant inheritance
Affected males with normal mates have
no affected sons and no normal
Both male and female offspring of
female carriers have a 50% chance of
inheriting the trait
For rare phenotypes, affected females
are more common than affected males
(fetal loss of affected males)
Complications leading to hardto-interpret pedigrees
Contiguous gene syndromes
Locus heterogeneity
Allelic heterogeneity
Penetrance and expressivity
Germ-line mosaicism
Imprinting effects
Age of onset