Medical and Molecular Genetics
Lecture 8 Single Gene Inheritance
1) Define and recognize examples of the following terms: locus, genotype,
phenotype, allele, homozygote, heterozygote, hemizygote, genetic heterogeneity,
variable expression, pleiotropy, reduced penetrance, consanguinity.
Locus – the position of a gene on a chromosome
Genotype – the genetic constitution of an individual
Phenotype – the observable trait(s) or characteristic(s) of an individual
Allele – alternate forms of a gene found at the same locus on homologous
chromosomes, segregating at meiosis one given to an individual form each parent.
Homozygote – has two identical alleles at a locus.
Genetic heterogeneity – a term used to describe the phenomenon where the same
phenotype is caused by different genotypic abnormalities.
Variable expression – occurs when individuals with the same genotype have different
phenotypes.
Pleiotropy – genes that have several different effects, when mutant genes produce
their effects on multiple organ systems and functions.
Reduced penetrance – a feature of autosomal dominant conditions where one either
shows some features of the genotype or none at all.
Consanguinity – couples who are related
2) Recognize and reproduce the pedigree symbols used to describe the family
relationships.
3) Distinguish between allelic and locus (non-allelic) heterogeneity. Allelic
heterogeneity is said to occur when the abnormal phenotype is caused by different
mutations at the same locus, whereas locus (non-allelic) heterogeneity is used to
describe a situation where a particular phenotype can be the result of mutations at two
or more separate loci.
4) Interpret the type of inheritance pattern represented by autosomal dominant,
autosomal recessive, X-linked dominant and X-linked recessive disorders, given
a medical history and pedigree. Autosomal dominant inheritance is expressed in
homozygotic dominant people and heterozygotes but not in homozygotic recessive
people. It is seen in every generation where children of an affected parent have a 50%
chance of inheriting the trait, but from an unaffected parent there is no chance, and
sex plays no role. Autosomal recessive inheritance is less common because it is only
seen in homozygotic recessive people. It generally appears only in the sibship of the
proband with a reoccurance of 25% and a 50% chance of being a carrier. Parents are
sometimes consanguineous, especially in rare disorders. X-linked dominant disorders
will appear in any affected male or female but a male child of an affected male parent
will not have the disease while the female will, and a male child of an affected female
parent will have at least a 50% chance of having the disease and a female child will
also have at least a 50% chance. X-linked recessive disorders will appear in any
affected males but will only appear in homozygous recessive females. An affected
father will have normal children but any daughters would be carriers for the disease.
An affected mother would have all carrier females and all affected males, but a carrier
mother would have half carrier females and half affected males.
5) Provide the risk of having an affected child for selected individuals in pedigrees
of autosomal dominant and recessive and X-linked dominant and recessive
inheritance.
Genotype
AA + AA AA + Aa
Aa + Aa Aa + aa
aa + aa
100%
100%
75%
50%
0%
Autosomal Dominant
0%
0%
25%
50%
100%
Autosomal Recessive
1
1
1
1
Genotype where
X Y+
X Y+
X Y+
XY +
XY +
indicates affected genes
X1X1
X1X
XX
X1X1
X1X
100%M
50%M
0%M
100%M
50%M
X-linked Dominant
100%F
100%F
100%F
100%F
0%F
100%M
50%M
0%M
100%M
50%M
X-linked Recessive
100%F
50%F
0%F
0%F
0%F
6) Describe the meaning and clinical implications of the Lyon hypothesis and its
relationship to carrier status in X-linked disorders. The Lyon hypothesis explains
dosage compensation, variable expression in female heterozygotes, and mosaicism.
Dosage compensation refers to the finding that females only express one allele of Xlinked genes even though they have two, so that they don’t produce twice as much as
males. Variable expression derives from the fact that inactivation of one X
chromosome is random, so although this favors a 50/50 split between maternal and
paternal, some women express more of one than the other thus having more mild or
more severe symptoms. Mosaicism is defined as having two different cell lines with
different genotypes, and this occurs in women due to the inactivation of one X in each
cell.
7) Provide examples of 4 clinical situations in which a female may manifest
completely an X-linked recessive trait. 1) Unfortunate Lyonization where a
heterozygous female has all or most of her X-chromosomes with the wild-type allele
inactivated, leaving only the mutant allele. 2) If a woman has only one X
chromosome. 3) A woman may be homozygous for the recessive allele. 4) Xautosome translocation may have translocated a portion of one of the X chromosomes
to another chromosome and would therefore remain active all the time.
8) Provide the possible ABO blood type of an offspring when given the ABO blood
type of both parents; and, provide possible parental blood types when given the
ABO type of their children.
AA
AO
BB
BO
AB
OO
100% AA 50% AA
100% AB 50% AB
50% AA
100% AO
AA
50% AO
50% AO
50% AB
50% AA
25% AA
50% AB
25% AB
25% AA
50% AO
AO
50% AO
50% AO
50% BO
25% AO
25% AB
50% OO
25% OO
25% BO
25% AO
25% OO
25% BO
100% AB 50% AB
100% BB 50% BB
50% AB
100% BO
BB
50% BO
50% BO
50% BB
50% AB
25% AB
50% BB
25% BB
25% AB
50% BO
BO
50% AO
25% AO
50% BO
50% BO
25% BB
50% OO
25% BO
25% OO
25% AO
25% OO
25% BO
50% AA
25% AA
50% AB
25% AB
25% AA
50% AO
AB
50% AB
25% AB
50% BB
25% BB
50% AB
50% BO
25% AO
25% AO
25% BB
25% BO
25% BO
100% AO 50% AO
100% BO 50% BO
50% AO
100% OO
OO
50% OO
50% OO
50% BO