Lecture 1- Genetic Diseases

Question 1

there are … protein-encoding genes in the human genome

Answer 1

19,000

Question 2

… refers to a permanent change in DNA

Answer 2

mutations

Question 3

Mutations affecting germ cells can be..

Answer 3

inherited

Question 4

Mutations affecting somatic cells may result in … or … abnormality

Answer 4

tumor

developmental

Question 5

3 types of mutations

Answer 5

point
frameshift
trinucleotide repeat

Question 6

A … mutation is when a single base is substituted

Answer 6

point

Question 7

A … mutation is when there is an insertion/deletion of 1-2 base pairs

Answer 7

frameshift

Question 8

A …. mutation is when there is amplification of a 3-nucleotide sequence

Answer 8

trinucleotide repeat (fragile X syndrome)

Question 9

3 other types of alterations other than mutations

Answer 9

polymorphisms

epigenetic changes

alterations in non-coding RNAs

Question 10

… disorders are diseases caused by single gene defects and they can be 3 different types:

Answer 10

mendelian

autosomal dominant
autosomal recessive
sex-linked (X -linked)

Question 11

do autosomal dominant disorders usually have outward physical changes?

Answer 11

yes but may be delayed onset

Question 12

In autosomal dominant disorders, …. is when a person has a mutant gene, but doesn’t or only partially expresses it phenotypically

Answer 12

reduced or incomplete penetrance

Question 13

In autosomal dominant disorders, … is when expression can be identified in all affected persons but to differing extents

Answer 13

variable expressivity

Question 14

In autosomal dominant disorders, … is when neither parent is affected of theres no family history

Answer 14

new or “de novo” mutation

Question 15

…. is an autosomal dominant disease with nearly 100% penetrance– and its relatively common (1/… live births) condition

Answer 15

Neurofibromatosis

3000

Question 16

T/F: Neurofibromatosis has highly variable expressivity

Answer 16

true

Question 17

… … disorders is the largest group of mendelian disorders

Answer 17

autosomal recessive

Question 18

affected patients of autosomal recessive disorders are…

Answer 18

homozygous

Question 19

In autosomal recessive disorders, …% of offspring are affected and …% of offsrping are carriers

Answer 19

25%

50%

Question 20

Many AR conditions are enzyme defects, leading to ….

Answer 20

metabolic dysfxn

Question 21

Age of onset for AR is usually… and … penetrance is common

Answer 21

early

complete

Question 22

Sex linked disorders are all on the … chromosome

Y chromosome only has 1 significant gene –

Answer 22

X

SRY sex determining region

Question 23

Most X linked disorders are …

Answer 23

recessive

Question 24

… is the process in which 16 days post conception, most (>75%) of one X chromosome is randomly inactivated (resulting in formation of a Barr body) in all of the cells within the zygote

Answer 24

Lyonization

Question 25

.... is when there is a random inactivation of an abnormally high number of normal X chromosomes resulting in X-linked disease expression in a heterozygous female

Answer 25

unfavorable lyonization

Question 26

... is an autosomal dominant disorder of connective tissue due to mutation of the FBN1 gene, resulting in abnormal fibrillin, a glycoprotein necessary for normal elastic fiber production

Answer 26

Marfan syndrome

Question 27

Someone who has the following traits have what disorder? ``` tall, thin abnormally long legs arachnodactly dislocation of eye lens aortic aneurym/dissec. ```

Answer 27

marfan syndrome

Question 28

At least 6 different types of .... syndrome may exist, probably because this is a problem of collagen synthesis, and there are about 30 different types of collagen

Answer 28

Ehlers-Danlos

Question 29

2 syndromes caused by mutations in structural proteins

Answer 29

marfan | ehlers-danlos

Question 30

Frequency of familial hypercholesterolemia is 1 in

Answer 30

500

Question 31

... is an autosomal dominant disorder that is a mutation of the gene that encodes the LDL receptor

Answer 31

familial hypercholesterolemia

Question 32

Patients with familial hypercholesterolemia have multiple... of the skin and premature ...

Answer 32

xanthomas | atherosclerosis

Question 33

Heterozygotes of FH have a .... increased amount of ...

Answer 33

2-3x | LDL

Question 34

Homozygotes of FH have over ... normal levels of LDL and often die of MI by 20 recent approval of .... to treat homozygous form

Answer 34

5x lomitapide

Question 35

3 diseases caused by mutations in enzyme proteins

Answer 35

phenylketonuria galactosemia lysosomal storage diseases

Question 36

Phenylketonuria is an autosomal .... disorder that affects 1 in .... caucasian infants

Answer 36

recessive | 10,000

Question 37

Phenylketonuria is a lack of .... that leads to ... and ...

Answer 37

phenylalanine hydroxylase hyperphenylalanemia PKA

Question 38

Affected infants of Phenylketonuria are normal at birth but elevated levels of phenylalanine impair... and ... is evident at 6mo. Screening in the US is mandatory

Answer 38

brain development mental retardation

Question 39

treatment of phenylketonuria

Answer 39

restricting dietary sources of phenylalanine intake will prevent mental retardation

Question 40

lysosomal storage diseases are by autosomal .... transmission

Answer 40

recessive

Question 41

mucopolysaccharide is a .... disease

Answer 41

lysosomal storage

Question 42

Mucopolysaccharide storage disease is due to lack of one of the several enzymes necessary to degrade

Answer 42

mucopolysaccharides

Question 43

affected patients of mucopolysaccharide of ten have...

Answer 43

coarse facial features cornea clouding joint stiffness mental retardation

Question 44

MPS type I disease is called.... and it is caused by a deficiency of ...

Answer 44

Hurler disease alpha-L-iduronidase (laronidase)

Question 45

The life expectency of Hurler disease is ... if left untreated

Answer 45

6-10 years

Question 46

.... or .... may improve outlook of Hurler disease but not all aspects of disease are corrected

Answer 46

bone marrow transplant enzyme replacement

Question 47

Cost of enzyme to trreat hurler disease can be about .... annually

Answer 47

300K

Question 48

... is MSP type II and is X-linked and is a deficiency of L-iduronate sulfatase. It is similar to Hurler as far as symptoms go except there is no cornea clouding and is milder overall

Answer 48

Hunter disease

Question 49

It's estimated that 1 in ... newborns have a chromosomal abnormality

Answer 49

200

Question 50

In as many as ... % of 1st trimester spontaneous abortions, the fetus has a chromosomal abnormality

Answer 50

50%

Question 51

The term ... means a normal chromosome count (2x23=46)

Answer 51

euploid

Question 52

The term.... is an increased chromosome count that is a multiple of that normally seen (3x23 or 4x23) and generally results in spontaneous abortion

Answer 52

polyploidy

Question 53

Any number that is not an exact multiple of the normal chromosome count is termed ... examples include an extra chromosome (trisomy, 2x23 +1= 47) and absence of a chromosome (monosomy 2x23-1=45)

Answer 53

aneuploidy

Question 54

... is transfer of a part of one chromosome to another nonhomologous chromosome (can be reciprocal)

Answer 54

translocation

Question 55

... is loss of a portion of a chromosome

Answer 55

deletion

Question 56

... is when a chromosome breaks in two points then the released fragment is reunited after a complete turnaround

Answer 56

inversion

Question 57

.... is most common of the chromosomal disorders and is associated with advanced maternal age

Answer 57

trisomy 21 (downs)

Question 58

If mother is younger than 20 then there is a 1 in ... chance of downs

Answer 58

1550

Question 59

If mother is older than 45 then there is a 1 in... chance of downs

Answer 59

25

Question 60

downs syndrome is due to meiotic non-disjunction of .... during ovum formation

Answer 60

chromosome 21

Question 61

Clinical manifestations of downs

Answer 61

mental retardation epicanthic folds (eyes slant down) flat facial profile cardiac malformations increased susceptibility to infection (early perio disease) large tongue increased rick (10-20x) of acute leukemia

Question 62

2 cytogenetic disorders involving sex chromosomes

Answer 62

Klinefelter syndrome Turner syndrome

Question 63

... is defined as male hypogonadism that develops when there are at least 2 X chromosomes and one or more Y chromosomes (most are 47 XXY)

Answer 63

Klinefelter syndrome

Question 64

The clinical manifestations of Klinefelter syndrome are...

Answer 64

increased length of lower limbs reduced body hair gynecomastia taurodontism

Question 65

... is due to partial or complete absence of one of the X chromosomes

Answer 65

Turner syndrome

Question 66

Clinical manifestations of turner syndrome

Answer 66

Short Webbing of neck/low posterior hairline Shield-like chest (broad) high arched palate congenital CV malformations failure to develop secondary sex charac.; primary amenorrhea

Question 67

Indications for prenatal genetic analysis

Answer 67

mother older than 34 parent is carrier of a chromosomal translocation or Xlinked disorder hx of previous child with chromosomal abnormality

Question 68

Indications for genetic analysis postnatally

Answer 68

multiple congenital anomalies unexpl. mental retard, or develop. delay suspected aneuploidy suspected sex chrom. abnormality infertility multiple spontaneous abortions