Week 3

Question 1

features of autosomal recessive disorders

Answer 1

parents are carriers, males and females equally affected, parents might share an ancestor if gene is rare

Question 2

modifier

Answer 2

gene or variant that modifies the expression of a phenotype assoc with a gene at a diff locus

Question 3

newborn screening

Answer 3

identifies conditions that can affect child’s long term health; early detection, diagnosis and intervention can prevent death and disability

Question 4

kennedy disease

Answer 4

spinar and bulbur muscular atrophy, repeat in androgen receptor = androgen insensitivity

Question 5

fragile x syndrome

Answer 5

worse in boys due to x inactivation, genetic disability, repeat –> hypermethylation of CpG upstream –> less FMRI protein translated. unstable repeats. anticipation = repeats enlarge with subsequent meiosis, so worsens with generations; in 5 prime UTR

Question 6

huntington’s disease

Answer 6

repeat in huntingtin gene in exon; causes poly glutamine which makes protein sticky; toxic gain of function

Question 7

friedreich ataxia

Answer 7

repeat in intron of frataxin –> causes abnormal DNA –> decreased frataxin mRNA and protein

Question 8

examples of anticipation

Answer 8

repeat expands over time; mytonic dystrophy, and fragile x syndrome

Question 9

familial anytrophic lateral sclerosis (ALS)

Answer 9

dominant; gain of function toxic, incomplete penetrance, genetic heterogeneity (variants in multiple genes), variable expresivity, founder effects, gene SOD I, mutant SOD can not make Cu/Zn dimer –> so sequesters wrong protein/oxidized

Question 10

classic ether danios sequence

Answer 10

dominant; haploinsufficiency, genetic heterogeneity, dominant negative effect; mutation in COL genes; affect fiber collagen formation, interferes with normal collagen

Question 11

myotonic dystrophy

Answer 11

muscle weakness; repeat in 3 UTR; toxic gain of function; mutant RNA forms nuclear aggregates and sequesters proteins like muscleblind; anticipation; autosomal dominant

Question 12

ALS

Answer 12

mutations in C9 gene; autosomal dominant; repeat in intron; could be gain of function or loss

Question 13

marfan syndrome

Answer 13

dominant; variable expressivity, 25% of it is de novo mutation, variance in FBN I for fibrillin I (fibers in extracellular matrix); connective tissue disorder; cant sequester TGF so starts a cascade and makes a protease that degrades the matrix; dominant negative because mutant protein interferes

Question 14

what are the 3 different kinds of mutations for de novo

Answer 14

new mutation in gamete made by the parent; made earlier during the development of the parent in a subset so could or could not be passed down; no mutation in parent and happens in embryo of child

Question 15

proteus syndrome

Answer 15

dominant; overgrowth of tissues; somatic variation occurs early in development embryo of child; variance in Glu17Lys in AKT 1; AKT is upregulator that is overstimulated

Question 16

Incomplete penetrance

Answer 16

Occurs when individuals carrying a pathogenic variant do not express the clinical features normally associated with pathogenic variants in the gene

Question 17

Variable expressivity

Answer 17

Individuals with a particular genotype known to cause disease can exhibit one to many clinical features of that disease and also vary in severity, from mild to sever

Question 18

Modifier

Answer 18

A gene or variant that modifies the expression of a phenotype associated with a gene at a different locus

Question 19

Somatic variant:

Answer 19

The variant is not inherited from a parent; the mutation arises randomly in one cell during the early stages of development before birth. The proportion of cells that carry that variant is dependent on which stage during development the variant occurs; earlier = more cells and tissues, later = fewer cells and even just part of tissues.

Question 20

Germline variant:

Answer 20

The variant is inherited from a parent, variant is present in every cell in the body.

Question 21

Dominant negative

Answer 21

Mechanism by which a protein with an altered sequence due to a pathogenic variant interferes with
the protein made from the other, unaltered allele. Thus, the negative effect of the pathogenic variant is amplified, and the function of both alleles is disrupted.

Question 22

Haploinsufficiency:

Answer 22

A loss of function variant where the protein made from the other, unaltered allele is unable to
compensate or prevent the disease.

Question 23

Gain of function

Answer 23

Mechanism by which a pathogenic variant increases the normal function of the protein.

Question 24

pyridoxine dependent epilepsy

Answer 24

recessive; ALDH7A1 deficiency –> PLP deficiency; vitamin B6 makes PLP and stops seizures; loss of function; inborn error of metabolism; compound heterozygous variants common

Question 25

Beta thalassemia

Answer 25

recessive; severe anemia; HBB variance; variable carrier frequencies; modifier alleles; genotype phenotype correlation -- some variants have a more severe phenotype; can be modified by HBA1 and HBA2 also by reducing alpha globin and increasing fetal beta globin (replacing the beta globin); leads to reduction of beta globin

Question 26

sickle cell disease

Answer 26

HBB missense Glu6Val

Question 27

cystic fibrosis

Answer 27

recessive; carrier frequencies vary between populations; newborn screening; modifier alleles; heterozygous selection advantage; variant in CFTR; chloride channel not functioning

Question 28

Hardy weinberg

Answer 28

P^2 + 2pq + q^2 = 1. P^2 is frequency of AA. q^2 is frequency of aa.

Question 29

spinal muscular atrophy

Answer 29

recessive; modifier alleles; newborn screening; gene duplications; deletion of exon 7 at SMN 1; but SMN 2 (copy) has a C to T mutation so it has exon 7; increased SMN 2 = milder disease

Question 30

x linked dominant

Answer 30

male to male transmission. males have more severe phenotype than females; if mom is carrier than males and females have equal chance of getting; if dad has it, then NO affected sons, because dads pass down Y. if dad has it, females will have it.

Question 31

x linked recessive

Answer 31

mostly males affected. heterozygous females are carriers and pass it down to males. can not be passed down from dad to his son. female can only have it, if both parents were carriers.

Question 32

linkage analysis

Answer 32

the closer the genes the higher the possibility of linked transmission

Question 33

high throughput or next generation sequencing analysis

Answer 33

all the genes in the genome can be simultaneously sequenced