Flashcards in Pattern of Inheritance II/III Deck (19):
What are the characteristics of autosomal recessive inheritance?
two mutant genes are required to cause disease, males and females affected equally,
child of affected person is (at least) obligate carrier
What’s the most common autosomal recessive disorder in Caucasians?
What’s the pathology of phenylketonuria (PKU)?
there’s a buildup of phenylalanine because there’s a shortage of the enzyme
(phenylalanine hydroxylase) that converts it to tyrosine; the disease is caused by
mutations in the PAH gene resulting in a primary deficiency of phenylalanine
hydroxylase; it’s autosomal recessive
What is the coefficient of inbreeding, F?
The probability that a homozygote has received both alleles at a locus from the same
True or false: For X-linked inheritance, all daughters of affected males are carriers and
all sons of affected males are “normal”. 50% of daughters of carrier females are carries
and 50% of sons of carrier females are affected.
What is lyonization?
The term used for the phenomenon of X inactivation. One X (either maternal or
paternal) is rendered transcriptionally inactive in somatic cells of females. It begins soon after fertilization (complete by 1st week). It’s randomly determined yet irreversible in somatic cells such that the inactive X in a particular cell remains inactive in all
descendants of that cell. The inactive X chromosome is heterochromatic (Barr body) and
heavily methylated at gene control regions
What lysosomal storage disease results from a deficiency in hexosaminidase A?
Tay-Sachs; it’s a neurodegenerative disease that presents shortly after birth and causes
death by 2-4 years old
What are characteristics of X-linked dominant disorders?
All daughters of affected males are affected, no male to male transmission, affected
woman have affected and unaffected daughters
What makes Y linked disorders easy to identify?
father passes it on to all his sons (ie Hypertrichosis Pinnae auris, Sertoli cell only
Describe the clinical manifestation of incontinentia pigmenti.
Progressive skin rash in linear distribution, conical teeth, alopecia
What are characteristics of X-linked recessive inheritance?
Disorder expressed almost exclusively in males. Females may manifest mild or no
phenotype. An example is Hemophilia A – Factor VIII deficiency
What are some characteristics of Duchenne Muscular Dystrophy? How does this
compare to BMD (Becker’s muscular dystrophy)?
Mutation in dystrophin gene on X chromosome resulting in proximal muscle
weakness, gower sign, pseudophertrophy of calf, elevated CPK, median age of death is
18 years. Becker’s is less severe – dystrophin protein still preserved. Female carriers
often have elevated CPK as well
What’s the most common form of inherited mental retardation? How is this similar to
Fragile X syndrome. Results in larger ears, relatively large chin, longer faces, larger
testes. Results from a triplet repeat expansion of FMR1 (5’ UTR), thus it’s a triplet
repeat expansion like Huntington’s. More repeats = more severe. Have fragile sites on the X chromsome
X-linked recessive phenotypes can happen in females if:
Skewed lyonization due to post-inactivation selection, variability in mosaicism, turner
syndrome (45, X), homozygosity for mutation (ie colorblind), X-autosome translocation
Describe the significant features of the mitochondrial genome. Talk about inheritance.
circular genome, encodes 13 proteins (imports the rest from the cytosol), the majority
of mitochondrial disorders are not caused by mutations in mitochondrial DNA—they are
caused by mutations in nuclear DNA. Follows matrilineal inheritance and thus mom
transmits to all kids, but her son doesn’t transmit to any of his kids
What happens when mitochondria fall prey to disease? Who is most affected?
When mitochondria fail, less energy (ATP) is generated within the cell and death
follows. Cells that are damaged the most are: brain, heart, liver, skeletal muscle, kidney,
and endocrine system
What is heteroplasmy as it pertains to mitochondrial inheritance? Threshold effect?
pertains to having different mitochondria within the cell. Threshold effect: symptoms
depend upon the percentage of mutant mtDNA. Intrafamilial variability
What is multifactorial/polygenic inheritance?
disorders or traits that result from complex interactions between many or few genes;
there is not a simple mendelian pattern of inheritance; for example: autism,
schizophrenia, diabetes type I/II, etc