Genetic Terms

Question 1

Compound Heterozygous

Answer 1

Both alleles are mutant, but at different points in the allele

Question 2

Hemizygous

Answer 2

Abnormal gene is on X chromosome in male patients

Question 3

Allelic heterogeneity

Answer 3

You have one phenotype, but a number of mutations on one locus can get you there

Question 4

Phenotypic Heterogeneity

Answer 4

You are looking at only one gene, and different mutations on that gene gives you different clinical phenotypes

Question 5

Locus heterogeneity

Answer 5

One clinical phenotype is brought upon by mutations in alleles at different loci

Example is long QT

Question 6

Plietropy

Answer 6

One gene affects multiple traits in multiple systems

VHL tumor

Question 7

Factors that can confound a pedigree

Answer 7

1. Early lethality
2. Small family size
3. Variable onset
4. Non-Mendelian inheritance

Question 8

Autosomal Inheritance Risk

Answer 8

Both parents must be heterozygotes

25%

Question 9

AR Risk that Unaffected Child Will be Carrier

Answer 9

66%

Question 10

AR Risk that Child will be carrier

Answer 10

50%

Question 11

Factors that affect the risk in AR disease

Answer 11

Consanguinity
Carrier frequency
Inbreeding
Genetic isolates

Question 12

Autosomal Dominant risk of Inheritence

Answer 12

50% in child of either sex

Question 13

Incomplete Dominance

Answer 13

Someone who is homozygous for an AD disorder will have a more severe phenotype than someone who is not.

Question 14

AD reduced penetrance

Answer 14

If the given genotype for disease has anything less than 100% phenotypic expressivity if heterozygous

ALL OR NOTHING

80% means that only 80% of people that have it show it

Question 15

Variable Expressivity

Answer 15

Between people in the population that have the mutation, severity can differ between two people

Question 16

Sex limited AD

Answer 16

Disease can be present in two sexes, but only one sex will express it

MPP is when LH is shut off in MALES ONLY

Question 17

X-linked inheritance

Answer 17

Hemizygous males and homozygous females are affected

NO MALE TO MALE TRANSMISSION

Question 18

Germline Mosaicism

Answer 18

When the parent is phenotypically normal, but has a mutation in the sperm or egg production

Question 19

Somatic Mosiacism

Answer 19

A mutation that does not happen in the Germline, but happens in the somatic cells of the embryo

Parents will be normal

Question 20

C-Value

Answer 20

Amount of DNA in one copy of the genome

Question 21

How to increase genome complexity/size

Answer 21

Duplication- of existing sequences. Followed by divergence and selection.

Incorporation-bringing in DNA from other species. Bacterial and viral DNA (lateral transfer)

Question 22

Conclusions from ENCODE

Answer 22

80% of DNA is functional

60-75% is translated into RNA

Question 23

Tandem Repeats

Answer 23

Create hot spots for recombination- inversion, duplication, deletion
Indicated in red/green color blindness

Question 24

Short Repeats

Answer 24

Satellite sequences- 100’s bp long, mostly at centromeres and telomeres
Micro satellites- used for genetic counseling. Few bp repeats

Question 25

Retrotransposons

Answer 25

1. RNA Pol II 2. Reverse Transcriptase 3. Integration LINE- mRNA encoding reverse transcriptase SINE-short mRNA transcript

Question 26

Pseudo genes

Answer 26

Copies of mRNA transcripts in the genome that stay inert because they do not have promoter sequences

Question 27

G banding

Answer 27

``` Giemsa dye P-short Q-long Acrocentric- high centromere position Can detect large structural changes 1 band= 45 genes ```

Question 28

FISH

Answer 28

Chromatin/chromosomes bound to slide and probes are used to hybridize by specific sequence You need to know what you are looking for

Question 29

Interphase FISH

Answer 29

Faster version, can be done anytime, lower resolution Prenatal diagnosis

Question 30

Metaphase FISH

Answer 30

Remember, shows issue in region SPECIFIC to probe Can look for smaller changes than interphase Resolution decreases as probes increase

Question 31

Comparative Genome Hybridization (CGH)

Answer 31

Array of Oligonucleotides specific to sequences immobilized on a chip Compare PCR amplified test to standard DNA Yellow means good expression, green means too much, red means too little

Question 32

CGH Defects

Answer 32

Can only detect quantity, not quality. You cannot see inversions or translocations because the sequence will be identical

Question 33

Translocation

Answer 33

Recip-Each chromosome changes and even amount of bases Nonrecip- when segment moves from one to another

Question 34

Identity of a chromosome

Answer 34

Identity of its centromere

Question 35

46 XY t(A:B) (q/pX;q/pY)

Answer 35

Normal number with a translocation between A and B in q arm X to Y

Question 36

45 XX -14 -12 +rob (14q;21q)

Answer 36

Robertsonian translocation at the q arms of 14 and 21, which causes monosomy at both chromosomes Often not lethal

Question 37

45 XX t(21;21) (q1.0;q1.0)

Answer 37

Isochrome translocation Viable but gametes receive either i21q (trisomy Downs)or no 21 at all (monosomy lethal)

Question 38

46 XX inv(6) (p23;q21)

Answer 38

Inversion on chromosome 6 within the chromosome between p23 and q21 Pericentric- different arms Paracentric- same arms

Question 39

46 XX dup(8)(q13;qter)

Answer 39

There is a duplication on chromosome 8 that takes the area between q13 and qter and repeats it adjacent.

Question 40

46 XY del19(q13.1;q13.3)

Answer 40

There is a deletion on chromosome 19 that takes away the area between q13.1 and q13.3

Question 41

Heritability

Answer 41

H=Variance DZ -Variance MZ/ Variance DZ DZ= brother sister MZ=identical twins 0= not due to heritability 1= completely due to heritability

Question 42

Multifactorial inheritance

Answer 42

Attributable to 2 or more genes, the environment, or both

Question 43

Functional polymorphisms vs mutations

Answer 43

FP are common in the population whereas mutations are not | FP are population risk, mutations are individual risk

Question 44

SNIP Panel

Answer 44

Looks for SNP's that are analogous to diseased alleles to find the alleles Same thing for finding the good alleles Probably ASO

Question 45

Rare variants in the human populations

Answer 45

Mutations

Question 46

Common variants in the human population

Answer 46

Functional polymorphisms

Question 47

Knock in

Answer 47

Replacing WT with a mutant gene

Question 48

Homeobox motifs

Answer 48

Rich in AT pairs | Only show specificity in vivo

Question 49

HOX gene order

Answer 49

3' head | 5' butt

Question 50

Hox A-P expression

Answer 50

Genes further 3' have further anterior boundary -spatial | Genes further 3' have earlier expression - temporal

Question 51

Anterior transformations

Answer 51

Due to loss of function mutations | 3' genes go further posteriorly

Question 52

Posterior transformations

Answer 52

Gain of function mutations | 5' gene gets revved up

Question 53

Formation of head structures

Answer 53

Otd- fly | Otx1/2- mammal

Question 54

Genes needed to revert to stem state

Answer 54

OCT4, SOX2, NANOG, C-MYC, KLF4

Question 55

Sonic hh necessity

Answer 55

Development of the CNS

Question 56

PKA

Answer 56

Phosphorylates Ci/Gli proteins for degradation

Question 57

Shh and CNS stem cells

Answer 57

Necessary for growth, proliferation, survival

Question 58

Mature hh protein

Answer 58

Cleaved and added cholesterol | Need action of DHCR7

Question 59

Axin, APC, DSK3

Answer 59

Work to degrade b-care in

Question 60

Dsh=Axin

Answer 60

Bind onto wnt-bound receptor | B-catenin lives on

Question 61

Gro

Answer 61

Inhibits b-catenin in wnt pathway

Question 62

PP2A

Answer 62

Takes P off of B catenin

Question 63

BTrCP

Answer 63

Proteosome for B catenin

Question 64

C-kit receptor

Answer 64

Expressed in neural crest cells | Follows steel ligand

Question 65

C-ret

Answer 65

Expressed by NCC in the gut | Follows GDNF

Question 66

T box genes

Answer 66

Encode TF's in NC cells

Question 67

Cancer contact inhibition

Answer 67

Cancer cells secrete metalloproteases that degrade the ECM and free up the cell to move

Question 68

Caretaker genes

Answer 68

Prevent or repair DNA damage | MLH, ERCC1, BRCA1

Question 69

Gatekeeper genes

Answer 69

Restrain division, induce apoptosis | P53

Question 70

Rb

Answer 70

Inhibits G1/S transition by inhibiting E2F

Question 71

P14ARF

Answer 71

Binds MDM2, which will stabilize p53

Question 72

Oncogenic mutations

Answer 72

Dominant-gain of function | Recessive-loss of function

Question 73

TGF and replication

Answer 73

Leads to a pathway that gives CDK inhibitor

Question 74

Activation of oncogene examples

Answer 74

C-Myc: overproduction due to replication/translocation C-abl: mutation provides self activation C-ras: mutations prevent inactivation