Genetic Disorders I

Question 1

SNP

Answer 1

variation at single nucleotide

Question 2

CNV

Answer 2

copy number variation

-large stretches of DNA that are repeated

Question 3

genomics

Answer 3

study of all genes

Question 4

epigenetics

Answer 4

heritable changes not caused by changes in sequence

Question 5

proteomics

Answer 5

study of proteins expressed in cells

Question 6

miRNAs

Answer 6

inhibit gene expression

Question 7

Dicer

Answer 7

cuts pre-miRNA

Question 8

RISC

Answer 8

RNA inducing silencing complex

-complexed with miRNA to decrease gene translation

Question 9

siRNA

Answer 9

therapeutic

Question 10

most common cause of genetic disorders

Answer 10

multigenic disorders

• caused by complex interactions of variant forms of genes
• polymorphisms

Question 11

missense

Answer 11

mutation alters meaning of sequnence

conservative - causes little change with AA switch
nonconservative - very different AA switch

Question 12

sickle mutation

Answer 12

glutamic acid to valine in beta-globin of Hg

-causes sickle cell anemia

Question 13

nonsense

Answer 13

encodes a stop codon

Question 14

frameshift

Answer 14

alter reading frame

Question 15

trinucleotide repeat mutations

Answer 15

amplification of sequence of three nucleotides

fragile x syndrome

Question 16

fragile x syndrome

Answer 16

trinucleotide repeat mutation

-familial mental retardation 1 (FMR1)

Question 17

mendelian disorders

Answer 17

mutation in single gene

Question 18

codominant

Answer 18

full expression of both alleles in heterozygote

Question 19

CCR5

Answer 19

used by HIV to enter cell

Question 20

genetic heterogeneity

Answer 20

multiple different mutations lead to same outcome

Question 21

pleiotropism

Answer 21

multiple end effects of single mutant gene

Question 22

incomplete penetrance

Answer 22

individuals with mutant gene do not show phenotype

Question 23

variable expressivity

Answer 23

trait caused by mutant gene is expressed differently

Question 24

sperm of old men

Answer 24

can get autosomal dominant mutations

Question 25

autosomal dominant

Answer 25

often loss of function - nonenzyme proteins - structural proteins

Question 26

marfan syndrome

Answer 26

autosomal dominant | -affect of skeletal system

Question 27

ehlers-danlos syndrome

Answer 27

autosomal dominant | -affect skeletal system

Question 28

famililal hypercholesterolemia

Answer 28

autosomal dominant | -mutation in LDL receptor

Question 29

huntington disease

Answer 29

autosomal dominant - gain of function - huntingtin protein - toxic to neurons

Question 30

onset of dominant vs. recessive?

Answer 30

dominant later in life | recessive earlier in life

Question 31

autosomal recessive

Answer 31

often enzymes affected

Question 32

lysosomal storage diseases

Answer 32

autosomal recessive

Question 33

glycogen storage disease

Answer 33

autosomal recessive

Question 34

alkaptonuria

Answer 34

autosomal recessive

Question 35

G6PD deficiency

Answer 35

X-linked - predispose RBCs to hemolysis - often in males anemia with malaria medication

Question 36

Vit-D rickets

Answer 36

X-linked dominant

Question 37

alpha-1 antitrypsin deficiency

Answer 37

decreased alpha-1 antitrypsin - missense mutation - leads to decreased metabolism of neutrophil elastase emphysema and liver disease

Question 38

cystic fibrosis

Answer 38

genetic defect in chloride ion channels

Question 39

marfan syndrome

Answer 39

disorder in CT elastin - skeletal, ocular, cardivascular problems - reduced elasticity - autosomal dominant defect in fibrillin 1 (FBN1)

Question 40

fibrillin-1

Answer 40

mutated in marfan syndrome

Question 41

clinical features of marfan

Answer 41

``` tall stature, long extremities long fingers and toes (arachnodactylyl) joint laxity long head (dolichocephaly) spinal deformities dislocated lenses (ectopia lentis) mitral valve prolapse striae skin ``` Dx: -two out of four system involvement (cardiovascular, skeletal, ocular, cutaneous), with minor of one other

Question 42

arachnodactylyl

Answer 42

long fingers and toes | -seen in marfans

Question 43

ehler-danlos syndrome

Answer 43

defect in synthesis or structure of fibrillar collagen -has 6 variants fragile skin, hypermobile joints, rupture of colon and large arteries

Question 44

mitral regurgitation

Answer 44

in marfan syndrome

Question 45

lysyl hydroxylase

Answer 45

autosomal recessive mutation - cross-linking of collagen IV -leads to kypohoscoliosis type of EDS type VI

Question 46

COL3S1

Answer 46

autosomal dominant mutation - collagen type III -vascular type of EDS type IV

Question 47

COL1A1 and COL1A2

Answer 47

autosomal dominant mutation - defect in conversion of procollagen to collagen in arthrochalasia type of EDS type VIIa, b

Question 48

COL5A1 and COL5A2

Answer 48

autosomal dominant mutation - collagen type V classical type of EDS type I and II

Question 49

familial hypercholesterolemia

Answer 49

mutation in LDL receptor -increases LDL in plasma increased scavenger receptor cholesterol pathway -xanthomas and premature atherosclerosis

Question 50

cholesterol metabolism

Answer 50

VLDL released from liver -cleaved at fat or muscle cells - become IDL IDL circulate with B-100 and E apoproteins - taken up by LDL receptor in liver - some converted to LDL LDL in plasma removed by - liver - scavenger receptor

Question 51

LDL mechanism into liver

Answer 51

``` bind receptor taken in as coated pit fuse with lysosome enzyme degradation leaves lysosome - via NPC1 and NPC2 ```

Question 52

cholesterol feedback

Answer 52

supress cholesterol synthesis activate esterification and storage of cholesterol supress synthesis of LDL receptor

Question 53

mutation in synthesis of LDL receptor

Answer 53

class I

Question 54

mutation causing LDL receptor in ER

Answer 54

class II

Question 55

mutation causing LDL receptor that can't bind

Answer 55

class III

Question 56

mutations causing LDL receptor that cannot form coated pits

Answer 56

class IV

Question 57

mutations in LDL recycling

Answer 57

class V

Question 58

classes of familial hypercholesterolemia

Answer 58

Class 1-5 ``` 1 - synthesis 2 - transport 3 - binding 4 - clustering 5 - recycling ```