Exam 2

Question 1

3 types of DNA repair

Answer 1

1. DNA mismatch repair: errors cause some cancers
2. Double-stranded DNA breaks: errors can cause breast/ovarian cancer
3. Nucleotide excision (NER): pyrimidine dimer removal. Errors cause xeroderma pigmentosum

Question 2

Xeroderma Pigmentosum

Answer 2

• Failure of NER system due to mutation in one of the 28 genes
• 2 hit hypothesis occurs:
  
  • Germline mutation (NER machinery inherited)
  • Somatic mutation (skin cell, pyrimidine dimer)

Question 3

Mutation rates

Answer 3

1. Each gamete = 30 new mutations anywhere in genome (somatic)
2. Large genes (# of base pairs) effected more (transcribed DNA)
3. Mutation hot spots - CG, cytosines methylated (Osteogenesis Imperfecta)
4. Parental age
   
   1. Mom: increased chromosomal disorders
   2. Dad: increased single-gene disorders (Marfan syndrome)

Question 4

ABO system is encoded on a single gene on what chromosome?

Answer 4

chromosome 9

Question 5

What are the 3 types of alleles for ABO typing

Answer 5

I^A, I^B, I^O

Question 6

5 types of DNA analysis

Answer 6

1. Restriction enzymes
2. Southern blot
3. Polymerase chain reation (PCR)
4. DNA sequencing
5. Microarray analysis

Question 7

Restriction enzymes

Answer 7

• Isolated from bacteria
• Cleave DNA at specific sequences (restriction sites).
• Analyzed with gel electorphoresis
• Wide variety of applications
• Can detect point mutations

Question 8

Southern blot

Answer 8

Limited to testing one mutation at the DNA level

Question 9

Polymerase chain reaction (PCR)

Answer 9

• Uses DNA polymerase on specific primers to amplify a gene
• Limited to testing for a few mutations
• Also detects expression differences, insertions/deletions, and tandem repeats

Question 10

DNA sequencing

Answer 10

Can detect mutations based on the DNA sequence

Question 11

Microarray analysis

Answer 11

• Can detect mutations at the DNA level
• Detects expression differences
• Similar to PCR but on a larger scale

Question 12

Allele-specific oligonucleotide (ASO) hybridization

Answer 12

• Short piece of synthetic DNA complementary to the sequence of a variable target DNA
• Used to hyridize with a pts DNA and shows that they have that specific nucleotide

Question 13

2 types of protein analysis

Answer 13

1. Protein electrophoresis
2. HPLC - high performance liquid chromatography (protein)

Question 14

DNA Polymorphisms

Answer 14

• Different class of DNA analysis
• Polymorphism: genes that have multiple alleles are polymorphic (ABO system: I gene)
• DNA sequence variants known to occur in certain populations/families and may influence risk for certain diseases
• Used to track disease when unsure which alleles are causing it

Question 15

3 types of DNA Polymorphisms

Answer 15

1. Single nucleotide polymorphisms (SNPs): assayed with restriction enzymes - Restriction fragment length polymorphisms (RFLPs)
2. Tandem repeat polymorphisms (3 nulceotides)
3. Copy number variants (CNVs) (large chunk of nucleotides)

Question 16

Monogenic vs Polygenic

Answer 16

Single gene vs Combination of genes

Question 17

Principle of Segregation

Answer 17

• In an organism that has 2 copies, in sexual reproduction when producing gametes, those 2 alleles will seperate
• Occurs durin anaphase
• Offspring will recieve one copy if seperated properly

Question 18

Principle of Independent Assortment

Answer 18

• Genes at different loci are transmitted independently ex. (A,a) has no effect on (B,b)
• Genes close together on the chromosome are consifered linked and won’t follow rules of independent assortment
• Genes farther apart are more likely to assort independently during crossing over

Question 19

Cystic Fibrosis

Answer 19

• Autosomal recessive
• Only recessive homozygote affected

Question 20

Phenylketonuria (PKU)

Answer 20

• Can’t metabolize phenylalanine
• By eliminating phenylalanine from the diet, genotype will remain the same but phenotype will be normal
• Environment alters phenotype

Question 21

Draw pedigrees

Define proband

Answer 21

1st person in whom the disease is diagnosed in the pedigree

Question 22

Autosomal Dominant Inheritance

Answer 22

• Vertical transmission of disease
• Most individuals are heterozygous and mate with homozygous recessive
• Males and females affected and transmit equally
• Recurrence risk usually 50%
• Ex. Post axial polydactly

Question 23

Autosomal Recessive Inheritance

Answer 23

• Generation skipping is observed
• Males and females affected and transmit equally
• Consanguinity (related persons) observed
• Recurrence risk usually 25%
• Ex. Tyrosine-negative albinism

Question 24

Not rigid dominant/recessive diseases

Answer 24

• Achondroplasia (AD trait):
  
  • Homozygous ppl don’t survive past infancy (respiratory failure)
  • Most ppl affected are heterozygous
• _​_Familial isolated growth hormone deficiency (IGHD): recessive and dominant form
• B-thalassemia: recessive and dominant form
• Sickle cell disease (homozygous) vs Sickle cell trait (heterozygous)

Question 25

Probability in Genetics

Answer 25

* **Multiplication rule (“AND”)**: Rolling 2 different numbers (1/6 \* 1/6 = 1/36 ) * **Addition rule (“OR”)**: Rolling either of 2 numbers (1/6 + 1/6 = 2/6 = 1/3) * **Combination of both:** * Probability of having 2 children of the same sex * First: boy and boy (girl and girl) → ½ x ½ = ¼ * Then: either two boys or two girls → ¼ + ¼ = ½

Question 26

What is the probability of two heterozygous carriers for the Cystic Fibrosis mutation having three normal children and two children with CF?

Answer 26

Question 27

Allele Frequency – Hardy Weinberg

Answer 27

p = A q = a pq = Aa p x p = (p²) = AA q x q = (q²) =aa p x q = Aa

Question 28

What are the classic signs of a De Novo mutation?

Answer 28

* No previous family hx * Occurs in the gamete of the parent NOT the germline cell * Parent is not affected but their children are and can pass it to their offspring * Ex. Anchondroplasia

Question 29

What are the classic signs of Germline Mosaicism?

Answer 29

* Occurs in the germline cell of the parent * Presence of more than one genetically distinct cell line in the body * Parent not at risk for mutation but their offspring are all equally at risk * Ex. Osteogenesis Imperfecta

Question 30

Reduced penetrance

Answer 30

* Person who has a disease-causing genotype does not develop the disease phenotype * Ex. Retinoblastoma, 90% penetrance = .9 (145 ppl x .9 = 130 affected)

Question 31

Age-dependent penetrance

Answer 31

* Delay in the age of onset of a genetic disease * Ex. Huntington's disease

Question 32

Describe Variable Expression What are the 3 factors that can affect variable expression?

Answer 32

* Degree of sverity of the disease phenotype 1. Non-genetic environmental factors (diet, exercise) 2. Modifier genes: genes which affect or alter the expression of other non-allelic gene 3. Allelic heterogeneity: different mutations at the same locus cause the same phenotype Ex. Neurofibromatosis

Question 33

Describe Locus Heterogeneity

Answer 33

A disease that can be caused by mutations at DIFFERENT loci in different families Ex. Adult Poly-cystic Kidney Disease (APKD), OI, Alzheimers, Breast cancer

Question 34

Define Pleiotropy

Answer 34

Genes that have more than one effect on the body Ex. Marfan syndrome has mutation in fibrillin and effects the eye, skeleton, and cardiovascular system

Question 35

# Define Consanguinity What's the risk of consanguinity?

Answer 35

* Mating of related individuals * Causes an increased risk of autosomal recessive disorders in a family due to allele frequecies being high