MCM_Final_TBL9

Question 1

3 Types of Human Genetic Disorders

Answer 1

1. Single Gene/Mendelian Disorders
   
   • results from mutation in single gene
2. Large Scale Chromasomal Disorders
   
   • results from structural or numerical mutation in chromasomes
3. Mutagenic Disorders
   
   • results from polymorphism and environmental factors

Question 2

Independent Assortment

Answer 2

BETWEEN

• he looked at two pairs of contrasting traits (yellow or green and round or wrinkled)
• Genes assort independently during gamete formation
• All possible gamete combinations form with equal frequency

I.E ONE trait for being round vs wrinkled is independent of ANOTHER trait for being green vs yellow. (THE SORTING OF TRAITS IS INDEPENDENT OF EACH OTHER)

= genetic variation

Question 4

Independent Segregation

Question 5

Independent Segregation

Answer 5

• paired sister chromatids are seperated independently

Question 6

Point Muations

Answer 6

• Deletions or insertions of a single base
• Substitution of base (ie A → T)

1. Silent mutation: no different in phenotype
2. Nonsense: mutation makes a STOP codon
3. Missense: makes a DIFFERENT AA

Question 7

Trinucleotide-repeat mutations

Answer 7

insertion of many copies of a codon (usually containg G/C)

1. loss of gene function
2. toxic gain of function (via changes in protein structure)
3. toxic gain of function (via mRNA)

Diseases

1. Fragile X Syndrome
2. Fragile X Tremor Ataxia
3. Fragile X Associated Ovarian Insuffiency
4. Friedreich Ataxia
5. Huntington

Question 8

Tay-Sachs Disease

Answer 8

• four-base insertion in the hexosaminidase A (HEXA) gene = frameshift mutation
• makes different AA dequence = defect in protein function

Question 10

Fragile X Syndrome

Answer 10

• CGG Triplet
• transcriptional silencing
• loss of protein function

Question 11

Fragile X Tremor Ataxia & Fragile X Ovarian Insufficiency

Answer 11

• CGG Triplet
• transcriptional DYSREGULATION
• ACCUMULATION of toxic mRNA

Question 12

Friedreich ataxia

Answer 12

• GAA triplet
• transcriptional silencing
• loss of function

Question 13

Intro to Huntington Disease

Answer 13

• CAG triplet
• polyglutamine expansions + misfolding
• toxic gain of function

Question 14

Huntington’s Disease (in depth)

Answer 14

• autosomal DOMINANT w. age dependent penetrance
• gene effected: HTT encoding Huntington protein
• repeat of CAG +40
  
  • greater repeats = earlier onset
• repeats = long misfolded polyglutamine = protein clogs (nuclear inclusions) = neurodegeneration

Question 15

Fragile X Syndrome (in depth)

Answer 15

• X-linked with INCOMPLETE PENETRANCE
• gene effected: familial mental retardation FMR1 gene on X chromosome
• repeat: CGG
• 55-200 repeats = lowkey effected / 230+ repeats = full effected
• in the abscense of folate, the X becomes fragile and breaks
• most common cause of intellectual disability IN MALES
  
  • ​SECOND TO Down’s overall

Question 16

Codominance

Answer 16

• neither allele is dominant
• both alleles expressed in heterozygotes
  
  • EX) ABO blood groups or pink flowers

Question 17

Epistasis

Answer 17

• gene interaction:
  
  • expression of one gene makes or modifies the effect of another
• Ex) Bombay Phenotype: Type O blood
  
  • DOUBLE PUNNET SQUARE: albinism + fur color genes

Question 18

X-linked

Answer 18

• Inheritance pattern is different depending on which parent carries the trait.
  
  • Mother passes to all sons & ½ of daughters
  • Fathers passes to all daughter & NO SONS
• (ex) Duchenne Muscular Dystrophy

Question 19

Mitochondrial Heredity

Answer 19

• Mitochondrial DNA = double-stranded circular DNA inherited from mother
• mtDNA susceptible to mutations: No histones in mtDNA for protection, sad DNA repair mechanism, high concentrations of reactive oxygen bc of cell respiration

Diseases:

1. Myoclonic epilepsy and ragged-red fiber disease (MERRF)
2. Leber’s hereditary optic neuropathy (LHON)
3. Kearns–Sayre syndrome (KSS)

Question 20

Answer 20

Autosomal dominant

1. always appear in each generation.
2. Affected individuals all have affected parents.
3. appear equally in both sexes

Question 21

Answer 21

Autosomal recessive disorders

1. typically skip generations.
2. appear equally in both sexes.

Question 22

Answer 22

X- Linked Dominant VERY RARE

• For affected fathers, all their daughters will express (sons all fine)
• For affected mothers:
  
  • ½ of sons of affected heterozygotes mothers will express the phenotype.
  • All sons of affected homozygotes mothers will express the phenotype

Examples include Vitamin D–resistant rickets and Alport syndrome

Question 23

Answer 23

X-linked Recessive

Females will very rarely express but are carriers.

• 50% of male offspring will be affected
• 50% of female offspring will be carriers

Often only affected males arise in the pedigree of an X-linked recessive disorder.

Question 24

Answer 24

mtDNA Disorders

• b/c only the maternal mtDNA is passed, all the children of a female who has a mtDNA mutation will inherit the mutation.

Effected male will pass it to none of his children.

Question 25

Penetrance

Answer 25

Incomplete penetrance is when **less than 100% of the population** **with** a particular **genotype** *_expresses_* *_the associated phenotype_* ex) Split Hand Foot Malformation: **Only 70%** of the people who have the mutation exhibit the clinical defect. * in pedigrees, apparent skipping of generations

Question 26

Hardy Weinburg Law Assumes (5)

Answer 26

1. Equal rate of survival and reproduction (**no** **selection**) 2. **No** new alleles arise or created by **mutation** 3. **No** **migration** into or out of population 4. **Infinitely** **large** **population** 5. **Random** **mating** occurs

Question 27

Crisper-Cas 9

Answer 27

* using this **gene** **editing** technique to **mutate the blocke**r * used to treat **Sickle** **Cell** Disease and **Thalassemia** * **bring back fetal Hb** expression * **Zynteglo** treatment **Crispr**: **C**lustered **R**egularly **I**nterspaced **S**hort **Palindromic** **Repeats** **Cas9**: **nuclease** that **cuts DNA** at the location that base pairs with the guide RNA

Question 28

CART-T

Answer 28

* T-Cells have adapted imune cell w/ specfici antigen receptors * **T-cells are "loaded" with SYNTHETIC ANTIBODIES** and immune stimulated domains (Ex) Treat **B-Cell Acute Lymphoblastic Leukemia** * **CAR-T** therapies target **CD19**, cell surface **marker** of **B-cells** * FDA: **Yescarta** and **Kymriah**