Single Gene Disorders And Population Genetics

Question 1

What are the two general types of autosomal dominant disorders?

Answer 1

1. Loss of function

2. Gain of function

Question 2

What are some causes of loss of function mutations?

Answer 2

• Defects in structural proteins (collagen mutations in OI)

- defects in regulatory proteins (LDL receptor deficiency)

Question 3

Gain of function mutations

Answer 3

Gain of function mutations endow normal proteins with toxic properties (Huntington’s)

Question 4

What type of disorder is neurofibromatosis type 1?

Answer 4

Autosomal dominant

Question 5

What is the gene defect for neurofibromatosis type 1?

Answer 5

Mutation in a cell cycle regulatory proteins

Question 6

What is the incident of neurofibromatosis type 1?

Answer 6

1 in 3000

Question 7

An important genetic concept that is epitomized by NF type 1 is:

Answer 7

Variable expression, even within the same family.

Question 8

What is a hallmark of neurofibromatosis type 1?

Answer 8

Variable expression

Question 9

What remains constant in neurofibromatosis type 1?, what is the clinical diagnostic clue?

Answer 9

Lisch Nodules

Question 10

What type of disorder is Marfan Syndrome?

Answer 10

Autosomal dominant

Question 11

What is the gene defect of Marfan Syndrome?

Answer 11

A mutation in the fibrillin gene

Question 12

Marfan syndrome is a good example of a genetic principle called:

Answer 12

Pleiotropy

Question 13

When a single mutation affects multiple organ systems a common feature of many genetic diseases

Answer 13

Pleiotropy

Question 14

What are ocular abnormalities of Marfan Syndrome?

Answer 14

Myopia and detached lens

Question 15

What type of disorder is thalassemias?

Answer 15

Autosomal recessive

Question 16

What is the genetic defect of thalassemias

Answer 16

Imbalance in globin chain synthesis

Question 17

Where is thalassemias most prevalent?

Answer 17

Mediterranean sea, parts of africa, and southeast asia

Question 18

What are the two types of thalassemia

Answer 18

• alpha thalassemia

- beta thalassemia

Question 19

Results from insufficient synthesis of the alpha chain (B chain accumulates)

Answer 19

Alpha thalassemia

Question 20

Results from insufficient synthesis of the B-chain (A chain accumulates)

Answer 20

B-thalassemia

Question 21

Which type of thalassemia is more detrimental

Answer 21

B-thalassemia

Question 22

What benefit is there to having thalassemias?

Answer 22

Malaria resistance

Question 23

What does thalassemias cause?

Answer 23

Premature death of cells destined to become red blood cells-results in hemolytic anemia

Question 24

Males are said to be _____ for genes on the X chromosome

Answer 24

Hemizygous

Question 25

Males need how many copies of a defective X-linked genes to show symptoms?

Answer 25

One

Question 26

Phenotype issues from X-linked recessive are much more common in which sex?

Answer 26

Males

Question 27

What causes hemophilia A and B?

Answer 27

Absence of blood clotting factors

Question 28

What are the mutation types for hemophilia A and B

Answer 28

Deletions, nonsense, mutations, DNA inversions Severity related to mutation type

Question 29

What is the firs thing you notice in hemophilia

Answer 29

Prolonged bleeding episodes, may be first noticed at birth with prolonged bleeding from the cord or umbilical area, or circumcision

Question 30

What are some common features of hemophilia

Answer 30

- prolonged bleeding episodes - intracranial hemorrhage - easy bruising - hemarthosis

Question 31

Why is AIDS the most common cause of death for patients with hemophilia

Answer 31

They are treated with blood transfusions that has not had the viruses killed, sometimes AIDS is present. They don't kill the viruses in the blood because it disrupts clotting factors

Question 32

What is another term for X inactivation

Answer 32

Lyonization

Question 33

X inactivation

Answer 33

- genes on on X chromosome are unavailable for transcription - inactive X chromosome can be observed by EM as a highly condensed Barr Body in the nuclei of interphase cells - associated with highly methylated DNA

Question 34

X inactivation being incomplete

Answer 34

Some genes on the activated chromosome remain available for transcription

Question 35

What is the explanation why some female hyterozygotes with one mutant X chromosome can show symptoms of an X-linked recessive disease

Answer 35

X inactivation

Question 36

Rare cases of single gene disorders that do not manifest until later in life

Answer 36

Delayed age onset

Question 37

What are examples of delayed age onset diseases

Answer 37

Huntington disease -30-40 age of onset in first generation Myotonic dystrophy -30-40 in first generation

Question 38

When the same disease phenotype can be causes by mutation in different loci (in different genes)

Answer 38

Locus heterogeneity

Question 39

Example of locus heterogeneity

Answer 39

EDS (ehlers-danlos syndrome)

Question 40

What inheritance patterns can EDS display?

Answer 40

Autosomal dominant, autosomal recessive, X linked

Question 41

What are the characteristics of EDS autosomal dominant

Answer 41

Mutations in collagen genes

Question 42

What are the characteristics of EDS autosomal recessive?

Answer 42

Mutations in the lysyl hydroxylase

Question 43

What are the characteristics of EDS x linked (recessive)

Answer 43

Mutation in a copper-binding proteins (gene located on the X chromosome) leads to reduced copper availability in the serum; shopper is essential for the activity of lysyl oxidase (cross linking of collagen fibers)

Question 44

All genetic disease begin with a _________

Answer 44

New mutation

Question 45

In cases with a high mortality or low fertility rate, it is often due to a _______

Answer 45

New mutation

Question 46

This is particularly true with the autosomal dominant diseases and X linked recessive diseases, where the phenotype would be seen immediately (AD) or very soon (X-linked) in the pedigree

Answer 46

New mutation Immediately shows up in pedigree and are detrimental and hard to pass on, gets weeded out

Question 47

___________ refers to diseases where the most recent generations of affected individuals show an earlier onset and more severe symptoms than previous generations

Answer 47

Anticipation

Question 48

Anticipation refers to diseases where the most recent generations of affected individuals show:

Answer 48

- an earlier onset | - more severe symptoms than previous generations

Question 49

The effect of anticipation is most often associated with diseases cause by _____________

Answer 49

Trinucleotide repeat expansions

Question 50

What are some examples of anticipation

Answer 50

Fragile X syndrome, myotonic dystrophy, and huntingtons disease

Question 51

The severity of the disease and the age of onset are correlated directly with what?

Answer 51

The length (number of repeated) of the segment containing repeats )the size of the expansion)

Question 52

What will eventually happen with anticipation in later generations?

Answer 52

Although considered an adult disease, in later generations symptoms may first appear in childhood, due to expansion of the trinucleotide repeat

Question 53

Assumptions for Hardy Weignberg

Answer 53

- large population - random mating with respect to they genotype at a given locus - constant and predictable relationship between genotype freq and gene freq

Question 54

This allows us to use simple math to determine the genotype frequencies if we know gene frequencies (and vice versa)

Answer 54

Hardy Weinberg

Question 55

What do you use to find gene frequency?

Answer 55

Hardy weinberg

Question 56

What part of hardy weinberg do you use for gene freq?

Answer 56

p + q=1

Question 57

How do you use hardy weinberg to find genotype freq

Answer 57

``` Allele 1 = p Allele 2= q Freq of genotype 1/1 (pp): p^2 Freq of genotype 1/2 (pq): 2pq Freq of genotype 2/2 (qq): q^2 ``` P^2+2pq+q^2=1

Question 58

Hardy weinberg can estimate the carrier frequency of a rare disease of _____________ inheritance only

Answer 58

Autosomal recessive

Question 59

Example of hard weinberg carrier frequency in PKU with prevalence of 1 in 10,000

Answer 59

PKU is qq (recessive)= q^2=1/10,000 Q=square root (1/10,000)=1/100=0.01 P=1-q P=1-0.01=0.99 Gene freq are q=0.01 and p=0.99 pp=0.99^2=0.98 Pq=2pq=2(0.01)(0.99)=0.02 or 1/50 The number of carriers for PKU is about 1 in 50

Question 60

Quicker way of finding number of carriers in hardy weinberg with cystic fibrosis incidence of 1 in 25,000

Answer 60

Q=square root of (1/2500)=1/50=0.20 0.02x2=0.04 or 1/25

Question 61

Ulprimary source of all new genetic variation in populations

Answer 61

Mutation

Question 62

Do mutation rates differe very much from population to population?

Answer 62

No

Question 63

Influences gene frequencies by selecting for genes that promote survival or fertility (referred to as fitness)

Answer 63

Natural selection

Question 64

Exposed to gene selection more often, generally have lower gene frequencies than recessive disease genes that can remain hidden in heterozygotes

Answer 64

Dominant disease genes

Question 65

Do all recessive genes has low rates?

Answer 65

No, some have a very high rate - sickle cell anemia- 1in 50 births in africa - carrier rate about 1 in 3.5

Question 66

Why is the carrier rate so high for sickle cell anemia in Africa

Answer 66

Gives fitness to individual who live in area high in malaria

Question 67

Natural selection has a _______ advantage

Answer 67

Heterozygote

Question 68

Heterozygotes for the sickle cell mutation (carriers)

Answer 68

The plasmodium survives very poorly and those people generally escape the worst infection with malaria

Question 69

Heterozygotes for thalassemia mutations

Answer 69

Have some protection against malaria

Question 70

Heterozygotes for the cystic fibrosis mutation

Answer 70

Protected against typhoid fever

Question 71

Genetic drift

Answer 71

- occurs in populations with finite (Small) population size - can be particularly rapid in very small populations - also called founder affect

Question 72

Relatively rare alleles are Preston in higher abundance in a small, isolated population that goes on to colonize the area

Answer 72

Founder affect

Question 73

Example of founder affect

Answer 73

More cases of ellis van creveld disease (very rare autosomal recessive disease) are seen in old order amish than the rest of the world

Question 74

What type of disorder is ellis van creveld disease

Answer 74

Very rare autosomal recessive disease

Question 75

Symptoms of ellis van creveld

Answer 75

- polydactyl | - shirt limbed dwarfism

Question 76

What is ellis van creveld disease caused by?

Answer 76

Caused by defective EVC gene, unknown function

Question 77

__________ results in the exchange of genes among populations

Answer 77

Gene flow

Question 78

________ is being seen more frequently as many parts of the world become less isolated and breeding between different populations becomes more commonplace

Answer 78

Gene flow