Genetics Fom

Front 1

What type of pedegree?

Back 1

autosomal recessive

Front 2

How do you know if pedigree is showing autosomal dominant?

Back 2

a. Trait expected in every generation
b. Affected offspring has one affected parent
c. Unaffected individuals don't transmit
d. Both sexes can transmit to both sexes

Front 3

How do you know if pedigree is showing Autosomal recessive?

Back 3

a. Most affected individuals have normal parents
b. on average 1/4 siblings affected
c. occurrence is more likely with consanguinity

Front 4

How do you know if pedigree is showing X-linked recessive?

Back 4

a. unaffected males do not transmit the trait
b. All daughters of affected males are heterozygous carriers
c. Female carriers transmit affected allele to 50% of offspring (sons and daughters)

Front 5

which pedigree does this show?

Back 5

auto dominant

Front 6

Which pedigree does this show?

Back 6

Autosomal recessive

Front 7

What pedegree is shown?

Back 7

x-linked recessive

Front 8

What type of pedigree is this?

Back 8

x-linked recessive

Front 9

Define the following terms about genetics...
1. Penetrance
2. Variable expressivity

Back 9

1. not all individuals who have genotype express it
2. individuals with the genotype express phenotype of gene different

Front 10

What is the difference between disorders caused by single genes and multiple ones?

Back 10

Single genes can be mathematically calculated through punnet squares or HW, but with multiple factors it has to be done by shear numbers (1/200)

Front 11

Define the following terms about genetics...
a. Liability
b. Risk

Back 11

a. person's genetic predisposition to a disorder, but still needs an enviromental factor to cause it to occur
b. Risk is measured by how many "bad" genes that tend to show the disorder

Front 12

Define the following terms about genetics...
a. Threshold model of expression

Back 12

a. idea that the more genes you have compared to the rest of the population... the higher risk you go over the "threshhold" level that will make the disorder occur

Front 13

Define the following terms about genetics
a. random drift
b. founder effect

Back 13

a. random fluctuations in allele frequencies from generation to generations in a small population (A--> B, and no C's in small group, so C could easily die out)
b. Founder- small subgroup of a large population can trace a disease to first people in a certain area. Mutations stayed within group due to reproducing within small community

Front 14

Define the following terms about genetics...
a. active selection
b. passive selection

Back 14

a. Group of people purposely choose specific mates and keep genes in population
b. survival advantages are found in small group of people living similarly for long time

Front 15

Define the following terms about genetics
a. multifactorial inheritances
b. Consanguinity's role in multifactorial genetic disorders

Back 15

a. genes are independently inherited but not independently expressed (hair, skin color)... depends on environment and how many copies of however many genes carrying
b. Amount of blood relateness of offspring. The closer the related the more likely to have received some of the at risk genes

Front 16

What role does gender have in multifactorial inheritance?
What would you say about risk threshold of females if they were affected less?

Back 16

Sometimes it takes less at risks genes to be expressed on a male vs. female

risk threshold would be higher or more to the right on the graph. However they will transmit the condition and affect men

Front 17

Which mult. factor inheritance is more prevalent in men?
What two disorders are women more likely to get than men... ratio?

Back 17

5:1 Pyloric Stenosis, at risk of narrowing of stomach
Anencephaly- 1:2 male to female, when child has top neural tube forming spinal cord and brain dont develop in embryogenesis
Spina Bifida (3:4) m:f failure of neural tube to close at lower place

Front 18

Give an example of risk and severity...

Back 18

The more genes person has with the disorder, the worse the disorder...
Cleft lip- unilateral- subsequent siblings is 2.5%, but if bilateral lip and palate- subsequent siblings is 6.5%

Front 19

As a physician why would HW be used?
What are the HW equations?

Back 19

If heredity does not follow, it allows studies to figure out where or how disorder occured
p + q = 1
P2 + 2pq + Q2 =1

Front 20

HW problem: Galactosemia (AR) resulting from mutations in GALT gene occur at a frequency of 1:10,000. What is the frequency of carriers?

Back 20

q2= .0001
q=.01
p+.01=1
p=.99
2(.99)(.01)= .0198= 1/50 or 2%

Front 21

What is the basic five steps to cancer development?

Back 21

1. Normal cell
2. Increased growth
3. Increased changes
4. Benign tumor
5. Metastatsis occurs

Front 22

What is an oncogene?

Back 22

protein kinases that control proteins by phosphorylation which allows them to completely take over cell growth, differentiation, and translocation

Front 23

What is the role of the following genes?
a. APC-
b. RAS
c. DCC
d. TP53
e. PRL53

Back 23

a. loss leads to increased growth (early tumor supressor)
b. Mutation leads to intermediate stage adenoma
c. Loss leads to late stage adenoma
d. loss leads to carcinoma
e. if overexpressed it leads to metastasis

Front 24

What are three types of cancer resulting from translocation and what gene is translocated?

Back 24

1. Burkitt Lymphoma- c-MYC translocated to immunoglobulin gene
2. Carcinoma of Lung, breast, cervix- c-MYC is not neccesarily translocated but is amplified
3. CML (chronic myelogenous leukemia)- c-ABL translocated to BCR locus

Front 25

What cancers result from these translocations?
a. c-MYC- amplification
b. c-ABL translocated to BCR locus
c. c-MYC translocated to immunoglobulin gene

Back 25

a. Carcinoma of the lung, breast, cervix
b. CML
c. Burkitt Lymphoma

Front 26

What does loss of heterozygosity mean in development of mutations leading to cancer?

Back 26

It causes cell to become homozygous for the mutated gene and therefore express the cancer gene.

Front 27

How does loss of heterozygosity occur (5 examples)?

Back 27

a. non-disjunction and loss of Ch. 13
b. Mitotic recombination
c. Ch13q14 deletion: (Aa -->A-
d. Gene inactivation
e. Point mutation or small deletion: (Aa-->AA)

Front 28

What is the clinical presentation of retinoblastoma?

Back 28

a. no family history
b. no pain
c. Bilateral most cases
d. Strabismus- eye tumor
e. cross eyed
f. leukocoria- yellow glow

Front 29

What are the heritable vs nonheritable comparisons of Rb?

Back 29

1. Heritable
a. Bilateral
b. early onset
c. 20% family history
d. multiple primary tumors risked
e. multiple tumors else where likely
f. Evidence of auto dom
2.Non- Heritable
a. unilateral
b. late onset (2 years)
c. no family hx
d. No increased risk of secondary primary tumors

Front 30

What is the gene involved in Familial adenomatous polyposis, Hereditary nonpolyposis colorectal cancer, and Retinoblastoma? (Say one thing about each)

Back 30

a. FAP- gene is APC- tumor suppressor gene presents many polyps
b. HNPCC- gene is HNPCC no polyps
c. Rb- gene is Rb-1 eye tumors

Front 31

How is the Rb-1 inherited?
What is the difference between FAP and HNPCC

Back 31

as dominant but expressed as recessive
FAP vs. HNPCC-
FAP- shows more polyps at young age genetically dominant, has APC tumor supressor gene mutated, has a benign marker at CHRPE

HNPCC- no polyps, later onset, look for MMR (mismatch repair) MSH2, MLH1 due to 60% of CRC having those genes... dominantly genetic

Front 32

What is the following techniques of genetics for...
1. Southern Blotting
2. Northern Blotting
3. Western Blotting

Back 32

1. reading DNA
2. reading RNA
3. reading Proteins

Front 33

What is the role of p53 in the cell cycle and what are some clinical consequences of mutations to this gene?

Back 33

a. tumor suppressor gene that regulates the cell cycle
b. "known as guardian of genome"
c. activated DNA repair, can hold cell cycle at G1/S point
d. Also initiates apoptosis if problems are not fixed
If mutated and loses function all hell breaks loose

Front 34

What is this tree showing?

Back 34

HNPCC

Front 35

What is this picture showing?

Back 35

FAP

Front 36

What is this picture showing?

Back 36

FAP

Front 37

what was this picture showing?

Back 37

FAP

Front 38

What is this picture showing and what does it have to do with cancer?

Back 38

It is hypertrophy of the retinal pigment epithelium in CHRPE a benign marker of FAP

Front 39

What is this family history of and what mutated gene causes this?

Back 39

FAP the gene is APC

Front 40

What are the pointers pointing to? Also type would you call each chromosome?

Back 40

Pointers are pointing to P (above) centromere (black line in middle) Q (below) and from left to right (metacentric, submetacentric, acrocentric, and telocentric)

Front 41

What is this type of translation? Where does it occur (which chromosomes) and what does it often lead to?

Back 41

Robertsonian translocation- fusion of Q arms of acrocentric chromosome
usually involves 13,14,15, 21, 22 could lead to trisomy

Front 42

What cancer is forming here?

Back 42

Chronic Myelogenous leukemia (CML)

Front 43

What is a robertsonian translation and what does it lead to?

Back 43

Fusion of Q arms of acrocentric chromosomes, usually 13,14,15,21,22 often leads to trisomies

Front 44

What is cause of CML? What is translocation called?

Back 44

translocation between chromosome 9 and 22 --> t(9;22) (q34;q11)

Called philadelphia chromosome

Front 45

What two genes fuse to form CML?
What gene does CD2 regulate?

Back 45

BCR-ABL

ABL

Front 46

What kind of tumor is associated with B-lymphocytes and produces antibodies?

Back 46

Burkitt Lymphoma

Front 47

What causes Burkitts Lymphoma?
Which genes are translocated

Back 47

Reciprical translocation t(8;14) (q24;32)
c-MYC from 8 to 14 leads to uncontrolled mitosis

Front 48

What cancer is from t(8;14) (q24;32)?

Back 48

Burkitts Lymphoma

Front 49

What does this picture represent?

Back 49

Reciprical translocation... i.e. burkitts lymphoma

Front 50

What are the two types of Burkitts lymphoma and how do u know physically and biologically?

Back 50

1. Endemic- seen in africa enlarged mandible tumor- EBV strong association 10 million around 7 y/o
2. Sporadic- involves abdominal organs- around 11 y/o

Front 51

What are two advantages to using PCR?

Back 51

1. Quick abundant substrate for mutation detection strategies.
2. Detecting changes in DNA length, such as small insertions or deletions.

Front 52

What do restriction enzymes do and how do you identify? What are some examples?

Back 52

a. They cleave DNA at specific spots so when they are viewed you look for specific markers at certain spots...known as pallindromes ECO-R1

Front 53

Where would the restriction enzyme cut?

Back 53

If there is three codons and followed by its three that it would pair with cause A-T and G-C so GAATTC is like seeing pair inside out

Front 54

What is the significance of Microarrays?

Back 54

Shows in colors which genes are expressed in different people...
Allows to see if tumor expression is function of specific gene expression

Front 55

What is a SNP and significance to use in clinical medicine?

Back 55

Single necleotide polymorphism- when a single nucleotide differs between members of species or individual paired chromosomes
Clinical- single differences in gene could make individuals more predisposed to disease or matches that resist disease. It is the study of SNPs that is synonomous with individualized medicine.

Front 56

What is cytochrome P450 used for?

Back 56

Drug metabolizing enzymes that are used to make cholesterol steroids and other improtant lipids, contain a heme group

Front 57

What is medical significance of AmpliChip CYP450?
What do labels P450, CYP2D6, and mean?

Back 57

It can find out which P450 genes you have functioning.
Cytochrome p450 is supergene family
CYP= gene
2= Family number
D= Subfamily
6= specific gene

Front 58

What are four stains used for visualization of chromosomes?

Back 58

1. G-banding- stains AT rich
2. Q-banding- Stains AT rich with UV light
3. R-banding- Uses G but reverse image
4. Chromosome painting- labeling each individual pairs with colors

Front 59

Explain differences between genotype and phenotype...

Back 59

Genotype- reflects genetic composition of a person at a specific place (locus, gene, allele)
Pheno- defined by genotype and environment- alleles expressed

Front 60

Define the parts of a chromosome and how would you explain label Chr 16p11.2?

Back 60

P, Q are arms, regions is first number, bands are second number within region and sub-bands follow decimal
[Chromosome 16 1 region, 1 band sub band 2 arm p

Front 61

What is it called when there is a presence of an extra chromosome?
What is germline mosaicism?
What is mosaicism?

Back 61

- Chromosomal mosaicism
- Mutation that occurs in developing cells that is not part of parental cells
- Cells within an individual with different DNA complements, or more that one genotype

Front 62

How is the X chromosome inactivate?

Back 62

-Lyon's Barr Body hypothesis
- X-chromosome inactivating center (XIC) and proximal end of (Xq)
- There is XIST RNA that binds to X-chromosome to inactivate

Front 63

If one X is inactivated then why is it important?

Back 63

Still used for 15-20% of total gene expression

Front 64

What are someways changes in chromosome # can occur?

Back 64

1. Non-disjunction in MI or MII
2. Fertilization mistakes
a. Partial Mole- two sperm fertilize one egg to equal 69 XXY or XXX
b. Complete Mole- two sperm fertilize an empty egg== 46 XX or XY

Front 65

What is the lab presentations of complete vs. partial mole?

Back 65

a. complete- no maternal contribution, no fetal parts, hCG higher than partial,
b. partial- maternal and paternal parts- fetals parts present embryo is viable for weeks

Front 66

What shows vaginal bleeding, abdominal pain, excessive uterine englargment, fetus smaller than gestational age, and ovarian cysts?

Back 66

Mole! or Ovarian teratoma

Front 67

What is the difference between ovarian teratoma and mole?

Back 67

Teratoma- due to problem caused by all mom's genes
Mole- caused by double copy of Dad's genes

Front 68

What are the types of trisomys on non-sex chromosomes?

Back 68

a. 13
b. 18
c. 21

Front 69

How would you write trisomy 21 or 18? (for male)

Back 69

47, XY +21
47, XY + 18

Front 70

Compared to 18 and 21 what distinguishes presentation of 13?

Back 70

SEVERE! and nondisjunction 80% from maternal and MI
- cleft lip/palate
-patau syndrome

Front 71

What distinguishes 18 from other trisomy's?

Back 71

- clenched fist
-rocker bottom feet
-edwards syndrom
MII nondisjuction

Front 72

What distinguishes 21 from other trisomies?

Back 72

a. Simian crease
b. brushfield spots
c.

Front 73

What is the most common cause of spontaneous abortions?
What is a sign of posibility of having a translocation downs?

Back 73

trisomy 16

- many spontaneous abortions

Front 74

What does this pedigree show?

Back 74

translocation downs on 14

Front 75

What are clinical signs of Klinefelter's syndrome?

Back 75

a. elevated gonadotropic levels
b. infertility
c. small testes
d. gynecomastia- dude to High E:T level
e. XXY

Front 76

A woman comes in with hanging arm (cubitus valgus) and a shielded chest and non development of secondary sexual characteristics.... she is?

Back 76

45 X_
turners

Front 77

When a cystic hygroma develops in utero and the women born had short stature and micrognathia with no ovary development? whats ur diagnosis?

Back 77

Turners
X_

Front 78

You suspect patient to have turners and do a karyotype and find some Y chromosome... what cancer does she have a larger risk for?

Back 78

gonadoblastoma

Front 79

If non-disjunction occurs and mom gives u two chromosome and body tries to get rid of trisomy, but it gets rid of chromosome from Dad what is process called and disorder? What is process of trying to kill extra chromosome called?

Back 79

a. uniparental disomy (two chromosomes but both from one parent)
b. chromosome rescue

Front 80

In uniparental Disomy whats the difference between disomy and isosomy?

Back 80

Disomy- 2 chromosomes from same parent
Isosomy- 2 identical from same parent (non-disjunction in MII)

Front 81

What is Prader Wili Syndrom and Angelman Syndrom? How do you know which one it is?

Back 81

microdeletion syndroms (uniparental disomy) both on 15q11-15 deletion
- Identifying on genes depends if child has disomy from mother (prader willi) and father (Angelman Syndrome)

Front 82

If you compared a prader willi subject to a Angelman syndrom person... what differences would you look for?

Back 82

PW- short, fat, feeding problems who don't have vomiting reflex, hypogonadic, very awkward
AS- puppet like qualities very happy (angel like)