Genetics 3 Lecture

Question 1

Define multi-factorial disorders

Answer 1

Disorders with multi-factorial inheritance result from teh combined effects of two or more mutant genes combined with environmental factors

Question 2

What are characteristics of these disorders?

Answer 2

Risk of expression is conditioned by the number of mutant genes inherited
Environmental influences significantly increase the risk of expression
Risk of recurrence of the disorder in first-degree relatives in 2-7%
Risk of recurrence in subsequent pregnancies increases with the birth of each affected child

Question 3

Types of cardiovascular diseases?

Answer 3

Congential heart disease, ischemic heart disease, hypertensive heart disease (systemic and pulmonary), valvular heart disease, nonischemic (primary) myocardial disease

Question 4

What causes cardiovascular disease?

Answer 4

Complex interplay of genetics and environmental factors that disrupt networks controlling:

• • morphogenesis (myocyte survival)
• • biomechanical stress responses
• • contractility (electrical conduction

Question 5

What is type 1 diabetes?

Answer 5

Beta cell destruction

Leads to absolute insulin deficiency

Question 6

What is type 2 diabetes?

Answer 6

Insulin resistance with relative insulin deficiency

• Genetic defects of beta cell function causes lots of mutation
• Genetic defects in insulin processing or insulin action, caused by insulin gene and receptor mutations

Question 7

What are sites of expansion and the affected sequence in selected diseases caused by?

Answer 7

nucleotide repeat mutations

Question 8

Cause of Progressive Myoclonus Epilepsy?

Answer 8

Not strictly tri-nucleotide repeats

- Usually heritable DNA expands typically in the promotor region

Question 9

Define triple repeat mutations

Answer 9

Fragile X syndrome

• Mutation on the C
• – 200 CGG repeats, methylation of the promoter and activation –> mental retardation

Question 10

Define mutations in the mitochondrial genes?

Answer 10

Leber hereditary optic neurpathy
- Maternally inherited bc ova contains significantly higher number of mitochondria than spermatozoa–> blindness, neurological dysfunction, cardiac conduction defect

Question 11

What is genomic imprinting?

Answer 11

Uniparental disomy
Characterized by differential activation of maternal and paternal alleles of certain genes
–> Prader willi syndrome (deletion of arm of chromosome 15 affects paternal –> metal retardation, short stature, obesity)

Question 12

What is gonadal mosaicism?

Answer 12

affect cells destined to form gonads during early embryogenesis

Question 13

What are chromosomal disorders due to?

Answer 13

Alterations in the number of chromosomes
Alterations in the structure of the chromosomes
- Result from errors during cell division

Question 14

Define monosomy

Answer 14

Associated with on less chromosome

Question 15

Example of monosomy?

Answer 15

Turner syndrome

• Monosomy of X
• Lymph edema of neck, hand, and feet, broad chest, failure of chest development, ovaries fibrous, congenital heart disease

Question 16

Define trisomy

Answer 16

Associated with one extra chromosome

Question 17

Example of trisomy?

Answer 17

Down syndrome
Trisomy 21
- Flat faces, mental retardation, congenital heart disease, acute leukemia, premature Alzheimer’s

Question 18

Define mosaicism

Answer 18

Associated with one or more populations of cells, some with normal chromosomal complement, others with extra or missing chromosomes

Question 19

Define deletion

Answer 19

Loss of a terminal or interstitial segment of a chromosome

Question 20

Define translocation

Answer 20

Transfer of a segment of one chromosome to another

Question 21

Define isochromosome

Answer 21

Formed when on arm is lost and the remaing arm is duplicated

Question 22

Define Inversion

Answer 22

Rearrangement associated with two breaks in a chromosome, followed by inversion and reincorporation of the broken segment

Question 23

Define ring chromosome

Answer 23

Deletion affecting both ends followed by fusion of the damaged end

Question 24

What does the diagnosis of genetic diseases involves?

Answer 24

Cytogenetic or molecular analyses

Question 25

Define cytogenetic analysis

Answer 25

Microscopic analysis of the number and structure of chromosomes in individual cells that are associated growth, development and body functions

Question 26

What is a prenatal cytogenetic analysis?

Answer 26

Preformed on fetal cells obtained by amniocentesis or chorionic villus biopsy - Advabced naterbak age - A parent with a structural chromosomal abnormality - Previous child with chromosomal abnormality - A parent who is carrier of an X-linked disease

Question 27

What is Fluorescence In Situ Hybridization?

Answer 27

Interphase nuclei stained with a fluorescent probe that hybridizes to chromosome 20 - Each nuclees reveals three dots representing three copies of the chromosome - -- Normal cells only have 2

Question 28

What is postnatal cytogenetic analysis

Answer 28

``` Period after birth Performed on peripheral blood lymphocytes - Multiple congenital anomalies - Unexplained mental retardation - Suspected chromosomal abnormalities - Suspected fragile X syndrome - Infertility - Recurrent abortion ```

Question 29

Define Di George Syndrome

Answer 29

Deletion on chromosome 22

Question 30

Define chromosome painting

Answer 30

An extension of FISH using multicolor FISH in a child with an undetermined abnormality - Shows any difference in the chromosomes based on color

Question 31

Define molecular analyses

Answer 31

Two different approaches are applied to the diagnosis of genetic diseases by recombinant DNA technology

Question 32

Define direct gene diagnosis

Answer 32

Involving detection of the mutant gene

Question 33

Define indirect gene diagnosis

Answer 33

Involving detection of linkage of the disease gene with a harmless marker gene

Question 34

Define Polymerase Chain Reactions

Answer 34

``` Denature Anneal Extend Repeat (around 20 cycles) 2 > 4 > 8 > 16 > 32 ```

Question 35

Define southern blot analysis

Answer 35

``` Digest DNA Separate fragments Transfer for further analysis Synthesis labeled cDNA probe Hybridize denatured probe Wash the membrane ```

Question 36

Define restriction analysis

Answer 36

Detection of coagulation factor V mutation by PCR G --> A substitution in an exon destroys one of the two Mnl1 restriction sites -- Gives rise to two rather than three fragments

Question 37

What is Fragile X syndrome

Answer 37

All sons are normal, females are carriers In oogenesis, premutation expands to full mutation --> all sons are affected and only 50% of females affected are actually affected - Amplifications of the DNA by primers that flank the region affected by trinucleotide repeats generate products of different sizes when DNA from normal carrier males and affected individuals is compared

Question 38

PCR recognizes?

Answer 38

mutations that affect the length of the DNA

Question 39

Define oligonucleotide probe analysis

Answer 39

Used when the point mutation producing the abnormal gene does no alter any known restriction site - Two ons having the single base that differs --> hybridizes to the normal gene but not the other gene - - Detemine based on strength of binding

Question 40

Define microarray-based DNA sequencing

Answer 40

A low power digitized scan of a gen chip that is no larger than a nickel in size but is capable of sequencing thousands of base pairs of DNA A high resolution view of the gen chip illustrates hybridizaiton patterns corresponding to a stretch of DNA sequence (upper: wild-type.. lower: mutation)

Question 41

Define indirect gene diagnosis

Answer 41

Gene Tracking Takes advantages of variation sin DNA near a mutated gene - Result from differences in specific nucleotides or number of nucleotide repeats Site polymorphisms (restriction fragment length polymorphism) result from DNA polymorphism that give rise to fragments of different lengths in Southern blot

Question 42

Define Linkage Analysis

Answer 42

PCR based application to detect progeny carrying the disease gene - Useful in presymptomatic diagnosis of several genetic disorders (cystic fibrosis, huntingtons, polycycstic, fragile X syndrome)

Question 43

What are limitations of indirect gene diagnosis?

Answer 43

Several affected and unaffected family embers needed Key family members must be heterozygous for the polymorphism Length polymorphisms have multiple alleles, great chance of heteozygosity Recombination between homologous chromosomes --> loss of linkage between DNA polymorph and mutant