Lecture 2 - Inheritance Patterns Flashcards
_______ ______ is the existence of different mutant alleles of the same gene. ie 1 gene, multiple _____ that could cause disease
allelic heterogeneity;
mutations (ie CF)
what is locus heterogeneity?
mutations in different genes that produce the same phenotype
veterical transmission is seen in what kind of inheritance?
autosomal dominant (ie trait appears in each generation)
penetrance:
at population level, the fraction of individuals with a genotype known to cause a disease who ….
have ANY sign or symptom of disease
_____ = trait varies in expression of disease, from mild to severe
expressivity
_____ = one gene mutation contributes to multiple effects
pleiotropy
equation for penetrance?
number of affected (penetrant) individuals divided by total number of individuals with the mutation
equation for risk of offspring of obligate/affected carrier in an autosomal dominant mutation with incomplete penetrance:
chance offspring to receive mutant allele * penetrance
achondroplasia:
due to constitutive activation of _____ which _____ chondrocyte proliferation
fibroblast growth factor receptor 3;
inhibits
achondroplasia:
characterized by failure of _____ bone growth. large _____ and short _____.
effect on intelligence?
longitudinal
head, limbs;
none
achondroplasia:
mode of inheritance?
due a missense mutation causing conversion of ____ to ____ at the ____ position
autosomal dominant;
glycine to arginine, 380
ie Gly380Arg
DNA mutations:
transition =
transversion =
purine to purine (ie A to G) or pyrimidine to pyrimidine (ie ie C to T);
purine to pyrimidine or vice versa
achrondoplasia:
are most cases from sporadic mutation or from inheritance?
sporadic (ie over 80%)
____ _____ is when a trait inherited in a dominant manner is more severe in a homozygote than in a heterozygote. an example is _____
incomplete dominant (semidominant); achrondroplasia (Aalso familial hypercholesterolemia)
in _____, both alleles contribute to the phenotype of the heterozyote. an example is ____
codominance;
A and B blood types (Also alpha 1 antitrypsin deficiency)
BITE features of osteogenesis imperfecta (OI):
Bone fractures;
I (blue eyes);
Teeth imperfections;
Ear (hearing loss)
Type ___ OI is the most common. type ___ is the most severe and is usually due to ___ ____
1, 2;
new mutations
_____ when the contribution from a normal allele is insufficient to prevent the disease. an example is type ___ OI
haploinsufficiency; 1
type 1 OI:
____ mutation results in reduced amount of a structurally ___ protein. this causes ____ defects
null;
normal
mild
in a ____ ____ mutation, a heterozygote produces a nonfunctional altered protein that prevents the normal gene product from functioning. this occurs in ____ forms of OI
dominant negative;
severe
ie mutant collagen causes other normal collagen to become abnormal–>severe effects
marfan syndrome:
inheritance: autosomal ____ with _____ and variable ____. due to a defect the ____ gene, leading to defective ____
dominant, pleiotropy, expressivity;
FBN1, fibrillin
marfan:
fibrillin normally forms a sheath around ____.
elastin
marfan symtpoms:
skeletal = long extremities and fingers (_____), ____ joints, scoliosis.
eyes: lens ____ that is displaced ___;
cardio: ______ and _____
arachnodactly, lax;
dislocation, upward;
MV prolapse, aortic dissection
a ____ _____ is heterozygous for 2 different mutant alleles of a gene
genetic compound (compound heterozygote)
_____ is the presence of 2 or more cell cells that differ genetically but came from one _____
mosaicism;
zygote
in _____ mosaicism, mutation arises from mitotic errors AFTER fertilization, causing _____ expression
somatic; segmented
some cell types normal, some mutated
____ mosaicism is due to a mutation in a egg or sperm cell. it can result in multiple _____ offspring from a _____ parent
germline/gonadal;
affected, unaffected
example of disorder that is associated with mosacism:
mccune-albright syndrome
in ______ mosaicism, all cells in the offspring will have the mutation. in ____ mosaicism, only a certain group of cells will
germline, somatic
Neurofibromatosis 1 (NF1): chacterized by multiple \_\_\_\_\_, \_\_\_\_\_ spots, and \_\_\_\_ nodules which are small benign iris nodules. which of these symptoms is not seen in NF2?
neurofibromas, cafe-au-lait; lisch;
lisch is not seen
NF1 is characterized by an increased risk of optic nerve ____ and ______
gliomas, pheochromocytomas
in a patient with a very rare autosomal recessive condition, what should be considered?
consanguinity
alkaptonuria:
inheritance mode?
due to a deficiency of ____
classic symptoms?
autosomal recessive;
homogentisate oxidase;
BLACK urine on exposure in air, deposits in pigments in things
(due to accumulation of homogentisic acid)
alkaptonuria:
_____ is the name for black pigments depositing places;
can cause debilitating _____
ochronosis;
arthritis
what is the risk of an unaffected sibling being a carrier of an autosomal recessive disease when they have a sibling with the disease?
2/3
X-linked dominant:
males are _____.
affected males have _____ daughters and ____ sons.
females are usually _____. their children have a _____ risk of being affected
hemizygous;
no normal; no affected;
heterozygous, 50%
x-linked recessive:
males are _____. incidence in males is ____ than in females. all daughters of affected males are ____. heterozygous females may be affected to varying extents due to ____
hemizygous. much higher;
carriers; mosacism/lyonization
what is lyonization? what is produced as a result?
functionally, females are ____ for many X genes
inactivation of 1 X-chromosome, barr body;
hemizygous
bruton’s X-linked agammaglobulinemia is a good example of ____ selection. in this form, mutant alleles are preferentially inactivated in ____ cells, while all other tissues have a more balanced inactivation.
post-inactivation;
B
duchenne:
inheritance?
problems due to ____ mutations that cause a _____ _____ protein
x-linked recessive;
FRAMESHIFT; truncated/absent dystrophin
duchenne:
characterized by progressive _____ ____.
inability to rise without pressing thigh’s (_____ sign);
_____ of calf muscles.
elevated ____
muscle weakness;
gower;
pseudohypertrophy (replacement with fat);
creatine kinase
duchenne:
early death, often due to ____ ____. early death is called a ___ ____ disorder.
female heterozygotes have varied phenotypes due to ____
dilated cardiomyopathy;
genetic lethal;
skewed lyonization
dystrophin:
encoded by the ____ gene, the largest protein-coding human gene. it does what?
DMD;
anchors muscle fibers to the ECM
becker dystrophy:
due to ______ mutations in dystrophin gene, leading to a _____ protein. it is ____ severe than duchenne’s.
NON-FRAMESHIFT;
partially functional (ie NOT TRUNCATED);
less
epigenetic changes affect gene expression without changing the ____
primary DNA sequence
epigenetics:
heterochromatin is transcriptionally _____. it is (more or less) condensed. increased methylation or increased acetylation?
inactive;
more;
increased methylation
euchromatin is transcriptionally _____. it is ____ condensed and appears ____ on EM
active; less;
lighter
DNA methylation at ___ ___ represses transcription. _____ relaxes DNA coding, allowing for transcription
CpG islands;
acetylation
_____ is present on X chromosomes, and when active, inactivates it self. its RNA is associated with ____
X-inactive specific transcript (cis acting);
barr bodies
Rett syndrome is a ____ ______ disease that affects mainly ____. most cases are caused by a loss of function in _____
X-linked dominant;
girls;
MeCP2 (methyl CPG binding protein 2)
Rett syndrome:
usually appears around age ____.
symptoms include loss of ____ abilities, gait dysfunction, sterotypic ____ movements, and psychomotor regression
1;
verbal, hand
Rett syndrome:
normally, MeCP2 causes ______ of genes. loss of MeCP2 causes inappropriate ____ of genes.
inactivation, activation
