Basic Medical Genetics - Single Gene Diseases

Question 1

exact physical location of a gene on a chromosome is called what?

Answer 1

a locus

Question 2

Used when there are 2 or more variations of a gene in a population

Answer 2

an allele

Question 3

homozygous vs heterozygous?

Answer 3

homozygous - both alleles of the gene are the same

heterozygous - each allele of the gene is different

Question 4

genotpye refers to what?

Answer 4

particular combo fo alleles that a person has for some locus

Question 5

genotype is reflected in?

Answer 5

phenotype - expression of genotype - the observable traits

Question 6

five basic modes of inheritance?

Answer 6

autosomal dominant 
autosomal recessive
X-linked dominant
X-linked recessive
mitochondrial

Question 7

what is autosomal dominance?

Answer 7

The locus is on an autosomal chromosome (1-22) and only one mutant allele is required for expression of the phenotype

Question 8

what is autosomal recessive?

Answer 8

The locus is on an autosomal chromosome and both alleles must be mutant alleles to express the phenotype

Question 9

what is X-linked recessive?

Answer 9

The locus is on the X chromosome and both alleles must be mutant alleles to express the phenotype in females but only one has to be affected in males

Question 10

what is X-linked dominance?

Answer 10

The locus is on the X chromosome and only one mutant allele is required for expression of the phenotype in females

Question 11

what is mitochondrial inheritance?

Answer 11

The locus is on the mitochondrial “chromosome”

Question 12

stop codons?

Answer 12

UAA, UAG, UGA

Question 13

start codon?

Answer 13

AUG

Question 14

what is a missense mutation?

Answer 14

single base change in the gene that leads to a change in the codon that encodes for 1 amino acid (SNP) which substitutes in a different amino acid than original
drastically changes folding

Question 15

what is a nonsense mutation?

Answer 15

ribosome comes to stop codon, stops and mRNA drops off releasing a partially complete protein
results in a short and completely inactive protein or enzyme

Question 16

what is a frameshift mutation?

Answer 16

only single base inserted or deleted
as ribosome is reading mRNA reads correctly until this point and then everything after the incorrect point will also be incorrect

Question 17

what is an in-frame mutation

Answer 17

mutations involving multiples of 3 bases that have either been inserted or deleted
so everything before and after the deletion is normal but missing a section

Question 18

what is consanguinity? what does it result in?

Answer 18

marrying 1st cousin or closely related relative

results almost always in an autosomal recessive disease

Question 19

pattern of AD genes?

Answer 19

if one parent has AD dz trait then most likely some offspring will have it too
M and F affected roughly equally

Question 20

recurrence risk of AD dz?

Answer 20

50%, but if both parents are heterozygous the recurrence risk is 7% - rare and more severe

Question 21

representations of AD dzs?

Answer 21

familial hypercholesterolemia (mainly LDL receptor deficiency)
Huntington's dz
neurofibromatosis type 1
Marfan syndrome 
acute intermittent porphyria

Question 22

how are AR dzs passed down?

Answer 22

both parents have to be heterozygous - one dominant gene, one recessive gene and then unlucky offspring has chance to present with AR dz
or child can get one copy of the recessive gene and then keep passing it down

Question 23

4 AR dzs?

Answer 23

sickle cell anemia
cystic fibrosis
phenylketonuria
Tay-Sachs dz

Question 24

who carries x-linked recessive dzs? who is impacted?

Answer 24

females carry

males are more impacted by since they only have 1 copy of the X chromosome

Question 25

how common is it for a female to inherit an X-linked recessive dz?

Answer 25

very rare b/c would have to receive 2 mutant X chromosomes

Question 26

who are impacted by X-linked dominant dzs?

Answer 26

women and men but women impacted more because usu passed down through female gene line

Question 27

if pt presents w/broad forehead, elongated face, large prominent ears, strabismus, highly arched palate, hyperextensible joints, MVP, hypotonia and flat feet what dz is this most likely?

Answer 27

fragile X syndrome

Question 28

what is the MC inherited form of mental retardation? due to what? severity of dz correlates with what?

Answer 28

fragile X syndrome
due to unstable CGG repeat at Xq27
severity of dz correlates with # of CGG repeats

Question 29

what is X chromosome inactivation?

Answer 29

inactivation of one copy of the X chromosome in females b/c they have 2 copies
happens so that an overabundant amount of enzymes and proteins aren’t made

Question 30

what is a barr body?

Answer 30

inactivated x chromosome in females - largely random which will become inactivated

Question 31

who are impacted by the concept of mitochrondrial inheritance?

Answer 31

men and women
all offspring of an affected female are affected
none of the offspring of an affected male are impacted

Question 32

typical dzs of mitochondrial inheritance origin?

Answer 32

neuropathies and myopathies

Question 33

what is Leber hereditary optic neuropathy?

Answer 33

normal vision until 20-25 yo then b/l visual loss dt inadequate ATP

Question 34

what is MELAS?

Answer 34

mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes

Question 35

what is incomplete penetrance?

Answer 35

when some individuals who have the genotype for dz do not display the dz phenotypically

Question 36

how do you calculate penetrance?

Answer 36

by calculating the # of ppl who are known to have the dz genotype and express the dz phenotype

Question 37

what is pleiotropy? common feature of what?

Answer 37

when single dz causing mutation affects multiple organ systems and is a common feature of genetic dzs

Question 38

classification of Marfan Syndrome?

Answer 38

pleiotropic dz
autosomal dominant
caused by mutation in gene that encodes fibrillin (gives CT its stretchiness)

Question 39

what is imprinting?

Answer 39

refers to fact that a small number of genes are transcriptionally active only when transmitted by one of the two sexes
homologous locus in the other parent is rendered transcriptionally inactive
for imprinted loci it is normal to have only the maternal or only the paternal active

Question 40

pedigree patterns of ____ ______ dzs show every generation is affected.
in ____ ______ dzs every other generation is effected

Answer 40

pedigree patterns of autosomal dominant dzs show every generation is affected.
in autosomal recessive dz every other generation is effected

Question 41

in ______ dzs, males are affected and ______ (gender) are carriers

Answer 41

in x-linked dominant dzs, males are affected and females (gender) are carriers

Question 42

in _____ inheritance females are affected 2x as men

Answer 42

in x-linked recessive inheritance females are affected 2x as men

Question 43

_____ results in myopathies, M+F all offspring of the affected F are symptomatic but none from the M

Answer 43

mitochondrial dz results in myopathies, M+F all offspring of the affected F are symptomatic but none from the M

Question 44

what is anticipation?

Answer 44

pattern of inheritance in which individuals in the most recent generations of a pedigree develop a dz at an earlier age or with greater severity than do those in the earlier generations

Question 45

dz where anticipation is applicable?

Answer 45

Huntington’s

Question 46

Huntington’s is a result of what?

Answer 46

gain-of-function mutation on chromosome 4 and is an example of a trinucleotide repeat expansion d/o
normal Huntington genes have fewer than 27 CAG repeats in the 5’ coding region and number is stable from generation to generation

Question 47

in families who eventually present with Huntington’s dz premutations of how many repeats are seen?

Answer 47

27-35
but these individuals do not have dz yet
dz sxs develop in those with 39 or more repeats