Multifactorial Inheritance

Question 1

What are the classic single gene disorders?

Answer 1

Sickle cell
cystic Fibrosis
duchenne dystrophy

Question 2

what is a characteristic of Multifactorial traits?

Answer 2

• Trait does not demonstrate a simple mendelian pattern
• Familial aggregation
• More common among the close relatives of the proband and less common in relatives who are less closely related
• Environment also interacts with genotype to produce the final phenotype

Question 3

What is the model that tries to explain multifactorial traits?

Answer 3

Liability/threshold

attempts to describe a populations genetic and environmental susceptibility.

Question 4

What is liability?

Answer 4

all factors that contribute to the disease

Question 5

What is threshold?

Answer 5

The limit to which normal is defined.
Passing threshold will make them affected

Question 6

Liability in multifactorial diseases

Answer 6

Disease state is determined by both genes and environment

Question 7

What is this image of?

Answer 7

Liability model and familial aggregation

Question 8

What happens when there are bad genes in the liability and threshold model?

Answer 8

The curve is moved to the right- more of the population is above the threshold point

The threshold line moves to the left-in essence the same thing as more of the population is under the affected portion of the curve

Question 9

Relative Risk ratio

Answer 9

Prevalence of disease in relatives of affected person / prevelance of disease in general population

Question 10

What does the liability threshold model explain?

Answer 10

Explains the pattern of recurrence risk in families

Question 11

What is Pyloric stenosis? What does it mean is a female has it in regards to recurrence risk?

Answer 11

Hypertrophy of the muscle between the stomach and intenstines,causing it to narrow(stenosis) impeding gastric emptying.

More common in male babies

If a female child gets it, that means there is a higher reccurence risk f because the parents have more of the bad gene

Question 12

Symptoms of pyloric stenosis

Answer 12

Severe vomiting

palpation of the abdomen may reveal a mass in the epigastrium

may cause other problems such as dehydration and salt fluid imbalances

Question 13

What are tools for determing the effects of genetic versus environment?

Answer 13

• Population/migration studies
• Family studies
• twin studies
• adoption studies
• Association studies

Question 14

Population/Migration studies

Answer 14

Indicative of environmental factors.

Disease incidences differences between populations suggest a genetic basis for that disease.

Could be due to cultural/lifestyle differences.

Question 15

It is known that Asian women have a lower incidence of breast cancer than American women. The Asian women move to America and within two generations, their incidence increased to near american levels. What experiment/study is this an example of?

Answer 15

Population/Migration study.

Question 16

What is concordance?

Answer 16

Both twins have the same disease

Question 17

What is Discordance?

Answer 17

One twin has the disease, the other twin does not.

Question 18

Monozygotic Twin (M.Z)

Answer 18

Derived from a single ovum

Genetically identical

Question 19

Dizygotic Twins (D.Z)

Answer 19

Derived from two seperate ova but share intrauterine environment.

Have genome similar to being regular siblings.

Question 20

What is the relationship of concordance between M.Z and D.Z?

Answer 20

The greater the difference in concordance rate between M.Z and D.Z twins= greater genetic input.

Question 21

What are limitations to twin studies?

Answer 21

• May underestimate heritability
• M.Z do have SOME different genes(like mitochondrial genes) and epigenetic differences
  
  • also different accumulation of somatic mutations due to errors in mitosis
• Different environmental exposures
• Different genes in different twin pairs
  
  • Studies between different sets of twins may point to different contributors for same phenotype
• Ascertainment pairs
• Most studies do NOT specify the loci and alleles but how genotype and environment interact

Question 22

What is the purpose of Association Analysis?

Answer 22

To test the co-occurence of a specific allele at a marker locus and a trait in a population by comparing the frequency of an allele in patients and controls

Question 23

What is Genome Wide Association studies?

Answer 23

Compares the genome of people with an illness to unaffected people to identify associations between SNPs and phenotype.

Question 24

What are two types of neural tube defects?

Answer 24

Anencephaly and Spina Bifida

Question 25

Anencephaly

Answer 25

Under developed brain and incomplete skull

May have brain stem function

most do not survive more than a few hours after a birth

Question 26

Spina bifida

Answer 26

Incomplete closure of the spine

Repair may be done in utero or postnatally

can be variable in severity

Question 27

Spina Bifida and incidence rates

Answer 27

Incidence = (1 to 2) / 1000

Question 28

Spina Bifida: Evidence for genetics

Answer 28

A woman who has had one child with a neural tube defect such as spina bifida has ~3% risk of having another

Mutations in genes coding enzymes for folate metabolism

Question 29

Spina Bifida

Answer 29

• Supplementation of the mother’s diet with folate can reduce the incidence of neural tube defects by about 70%
  
  • The 3% risk of the woman having another child with a NTD can be reduced to 1% with high doses of folic acid