Lecture 2 - Inheritance Patterns

Question 1

_______ ______ is the existence of different mutant alleles of the same gene. ie 1 gene, multiple _____ that could cause disease

Answer 1

allelic heterogeneity;

mutations (ie CF)

Question 2

what is locus heterogeneity?

Answer 2

mutations in different genes that produce the same phenotype

Question 3

veterical transmission is seen in what kind of inheritance?

Answer 3

autosomal dominant (ie trait appears in each generation)

Question 4

penetrance:

at population level, the fraction of individuals with a genotype known to cause a disease who ….

Answer 4

have ANY sign or symptom of disease

Question 5

_____ = trait varies in expression of disease, from mild to severe

Answer 5

expressivity

Question 6

_____ = one gene mutation contributes to multiple effects

Answer 6

pleiotropy

Question 7

equation for penetrance?

Answer 7

number of affected (penetrant) individuals divided by total number of individuals with the mutation

Question 8

equation for risk of offspring of obligate/affected carrier in an autosomal dominant mutation with incomplete penetrance:

Answer 8

chance offspring to receive mutant allele * penetrance

Question 9

achondroplasia:

due to constitutive activation of _____ which _____ chondrocyte proliferation

Answer 9

fibroblast growth factor receptor 3;

inhibits

Question 10

achondroplasia:
characterized by failure of _____ bone growth. large _____ and short _____.
effect on intelligence?

Answer 10

longitudinal
head, limbs;
none

Question 11

achondroplasia:
mode of inheritance?
due a missense mutation causing conversion of ____ to ____ at the ____ position

Answer 11

autosomal dominant;
glycine to arginine, 380
ie Gly380Arg

Question 12

DNA mutations:
transition =
transversion =

Answer 12

purine to purine (ie A to G) or pyrimidine to pyrimidine (ie ie C to T);
purine to pyrimidine or vice versa

Question 13

achrondoplasia:

are most cases from sporadic mutation or from inheritance?

Answer 13

sporadic (ie over 80%)

Question 14

____ _____ is when a trait inherited in a dominant manner is more severe in a homozygote than in a heterozygote. an example is _____

Answer 14

incomplete dominant (semidominant);
achrondroplasia (Aalso familial hypercholesterolemia)

Question 15

in _____, both alleles contribute to the phenotype of the heterozyote. an example is ____

Answer 15

codominance;

A and B blood types (Also alpha 1 antitrypsin deficiency)

Question 16

BITE features of osteogenesis imperfecta (OI):

Answer 16

Bone fractures;
I (blue eyes);
Teeth imperfections;
Ear (hearing loss)

Question 17

Type ___ OI is the most common. type ___ is the most severe and is usually due to ___ ____

Answer 17

1, 2;

new mutations

Question 18

_____ when the contribution from a normal allele is insufficient to prevent the disease. an example is type ___ OI

Answer 18

haploinsufficiency; 1

Question 19

type 1 OI:

____ mutation results in reduced amount of a structurally ___ protein. this causes ____ defects

Answer 19

null;
normal
mild

Question 20

in a ____ ____ mutation, a heterozygote produces a nonfunctional altered protein that prevents the normal gene product from functioning. this occurs in ____ forms of OI

Answer 20

dominant negative;
severe

ie mutant collagen causes other normal collagen to become abnormal–>severe effects

Question 21

marfan syndrome:

inheritance: autosomal ____ with _____ and variable ____. due to a defect the ____ gene, leading to defective ____

Answer 21

dominant, pleiotropy, expressivity;

FBN1, fibrillin

Question 22

marfan:

fibrillin normally forms a sheath around ____.

Answer 22

elastin

Question 23

marfan symtpoms:
skeletal = long extremities and fingers (_____), ____ joints, scoliosis.
eyes: lens ____ that is displaced ___;
cardio: ______ and _____

Answer 23

arachnodactly, lax;
dislocation, upward;
MV prolapse, aortic dissection

Question 24

a ____ _____ is heterozygous for 2 different mutant alleles of a gene

Answer 24

genetic compound (compound heterozygote)

Question 25

_____ is the presence of 2 or more cell cells that differ genetically but came from one _____

Answer 25

mosaicism; | zygote

Question 26

in _____ mosaicism, mutation arises from mitotic errors AFTER fertilization, causing _____ expression

Answer 26

somatic; segmented | some cell types normal, some mutated

Question 27

____ mosaicism is due to a mutation in a egg or sperm cell. it can result in multiple _____ offspring from a _____ parent

Answer 27

germline/gonadal; | affected, unaffected

Question 28

example of disorder that is associated with mosacism:

Answer 28

mccune-albright syndrome

Question 29

in ______ mosaicism, all cells in the offspring will have the mutation. in ____ mosaicism, only a certain group of cells will

Answer 29

germline, somatic

Question 30

``` Neurofibromatosis 1 (NF1): chacterized by multiple _____, _____ spots, and ____ nodules which are small benign iris nodules. which of these symptoms is not seen in NF2? ```

Answer 30

neurofibromas, cafe-au-lait; lisch; lisch is not seen

Question 31

NF1 is characterized by an increased risk of optic nerve ____ and ______

Answer 31

gliomas, pheochromocytomas

Question 32

in a patient with a very rare autosomal recessive condition, what should be considered?

Answer 32

consanguinity

Question 33

alkaptonuria: inheritance mode? due to a deficiency of ____ classic symptoms?

Answer 33

autosomal recessive; homogentisate oxidase; BLACK urine on exposure in air, deposits in pigments in things (due to accumulation of homogentisic acid)

Question 34

alkaptonuria: _____ is the name for black pigments depositing places; can cause debilitating _____

Answer 34

ochronosis; | arthritis

Question 35

what is the risk of an unaffected sibling being a carrier of an autosomal recessive disease when they have a sibling with the disease?

Answer 35

2/3

Question 36

X-linked dominant: males are _____. affected males have _____ daughters and ____ sons. females are usually _____. their children have a _____ risk of being affected

Answer 36

hemizygous; no normal; no affected; heterozygous, 50%

Question 37

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 ____

Answer 37

hemizygous. much higher; | carriers; mosacism/lyonization

Question 38

what is lyonization? what is produced as a result? functionally, females are ____ for many X genes

Answer 38

inactivation of 1 X-chromosome, barr body; | hemizygous

Question 39

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.

Answer 39

post-inactivation; | B

Question 40

duchenne: inheritance? problems due to ____ mutations that cause a _____ _____ protein

Answer 40

x-linked recessive; | FRAMESHIFT; truncated/absent dystrophin

Question 41

duchenne: characterized by progressive _____ ____. inability to rise without pressing thigh's (_____ sign); _____ of calf muscles. elevated ____

Answer 41

muscle weakness; gower; pseudohypertrophy (replacement with fat); creatine kinase

Question 42

duchenne: early death, often due to ____ ____. early death is called a ___ ____ disorder. female heterozygotes have varied phenotypes due to ____

Answer 42

dilated cardiomyopathy; genetic lethal; skewed lyonization

Question 43

dystrophin: | encoded by the ____ gene, the largest protein-coding human gene. it does what?

Answer 43

DMD; | anchors muscle fibers to the ECM

Question 44

becker dystrophy: | due to ______ mutations in dystrophin gene, leading to a _____ protein. it is ____ severe than duchenne's.

Answer 44

NON-FRAMESHIFT; partially functional (ie NOT TRUNCATED); less

Question 45

epigenetic changes affect gene expression without changing the ____

Answer 45

primary DNA sequence

Question 46

epigenetics: heterochromatin is transcriptionally _____. it is (more or less) condensed. increased methylation or increased acetylation?

Answer 46

inactive; more; increased methylation

Question 47

euchromatin is transcriptionally _____. it is ____ condensed and appears ____ on EM

Answer 47

active; less; | lighter

Question 48

DNA methylation at ___ ___ represses transcription. _____ relaxes DNA coding, allowing for transcription

Answer 48

CpG islands; | acetylation

Question 49

_____ is present on X chromosomes, and when active, inactivates it self. its RNA is associated with ____

Answer 49

X-inactive specific transcript (cis acting); | barr bodies

Question 50

Rett syndrome is a ____ ______ disease that affects mainly ____. most cases are caused by a loss of function in _____

Answer 50

X-linked dominant; girls; MeCP2 (methyl CPG binding protein 2)

Question 51

Rett syndrome: usually appears around age ____. symptoms include loss of ____ abilities, gait dysfunction, sterotypic ____ movements, and psychomotor regression

Answer 51

1; | verbal, hand

Question 52

Rett syndrome: | normally, MeCP2 causes ______ of genes. loss of MeCP2 causes inappropriate ____ of genes.

Answer 52

inactivation, activation