Genetic Inheritance of Disease

Question 1

how much of genome is non-coding?

how many genese make up the coding part of genome?

Answer 1

• 98% is of human genome is non-coding

2% has 21 000 genes

Question 2

what are a) varients? b) polymorphisms? c) mutations

Answer 2

a) varients: changes in genome that do no affect human health

b) polymorphisms: genetic mutations that are very common in the human genome, may or may not contribute to disease (more than 1% freq)

c) mutations: less that 1% frequency in human populations and generally affect normal physiology

Question 3

what are two ways can classify a mutation?

Answer 3

• inherited or acquired
• rare or common

Question 4

what is a mendelian or monogenic disorder?

what is a multifactorial disorder?

what is a complex disorder?

Answer 4

mendelian / monogenic : a disease or trait determined by a single gene

multifactorial: disease / trait determined by a small no. of genes (oligogenic trait), or a large number of genes with individually small effects (polygeneic traits)

complex: disease or trait determined by a large number of genes and their effects is also altered by environmental factors (e.g. Diabetes)

Question 5

what is an allele?

Answer 5

alternative version of the same gene. one is inherited from the mother, one is from the father and can vary in sequence.

homozygous: both alleles are same from parents

heterozygous: if the alleles at a specific postion on a gene are not identical

Question 6

what does the mode of inheritance in Mendelian traits depend on?

Answer 6

1. whether the gene is on an autosomal or sex chromsome

2. whether the trait is determined by a dominant or recessive genotypes

Question 7

why is idea the of heterozygosity / homozygosity lost for sex linked mendelian traits?

Answer 7

because you dont have two copies of the same gene (X / Y) are different.

Question 8

what are the 5 main types of modes of inheritance?

Answer 8

autosomal dominant

autosomal recessive

X-linked dominant

X-linked recessive

Y-linked

Question 9

which offspring from autosomal dominant parents will not inherit disease?

Answer 9

homozygous recessive children.

(if you have allele you get the trait)

Question 10

what can modify the expression of autosomal dominant diseases?

(linked:) what is variable expressibivity?

what is anticipation?

Answer 10

1. new mutation: sporadic de novo cases

2. variable penetrance: genetic background or the environment can cause difference in disease penetrance

3. variable expressivity: variation is severity of symptoms (genes could be expressed at different level)

anticipation: disease manifests at a younger age in successive generations

(penetrance - proportion of individuals carry a disease causing allele)

(expressivity - extent to which a genotype exhibits its phenotypic expression)

Question 11

give example of autosomal recessive disease (x3)

which is more common - autosomal dom or autosomal rec?

Answer 11

phenylketonuria (PKU)

sickle cell disease

CF

autosomal recessive is more common

Question 12

how can you tell from a pedigree if a disease is autosomal recessive?

Answer 12

• more carriers than affected
• not sex linked (equally effects m/f)

Question 13

which offspring are affected x-linked dominant disease is given by:

a) affected mother
b) affected father

Answer 13

x-linked dominant:

if mother is affected: can pass onto boy or girl offspring

if father is affected: _pass onto all daughters, not sons (_gives son Y chr - unaffected)

Question 14

give 3 x-linked dominant traits

Answer 14

goltz syndrome

x-linked poryphyria

fragile x-syndrome

Question 15

on a pedigree, which shape is male and which is female?

Answer 15

male - square

female - circle

Question 16

• who is normally the
  a) carrier of x-linked recessive?
  b) affected offspring
• why does affected son not recieve it from father?

Answer 16

carrier: usually the mother

affected offspring: usually the son. female normally protected by dominant healthy x chr. v rare but if female is affected: mother is carrier and father is affected

(males are usually born to unaffected parents)

there is no father to son transmission because he gives the Y-chr not the X

Question 17

e.g. of x-linked recessive diseases?

Answer 17

hameophilia A andB

Hunter syndrome

Duchenne and Becker MD

Question 18

who is affected by Y-linked disease?

how does the transmission work in y-linked diseases?

what do most genes on Y chr involve? how many genes?

what are affected individuals called?

Answer 18

males onnly affected

father -> son transmission

200 genes on y chr. most are sexual characteristics

affected individuals are called hemizygotes

Question 19

what type of mutation is this ?

Answer 19

de novo

Question 20

what is the grey box in this and what type of diseas e

Answer 20

autosomal dom

grey - anticipation

Question 21

what are factors that affect allele frequencies in a pop?

Answer 21

pop size

mutation rate

genetic drift

natural selection

environment

migration

non-random mating

Question 22

describe difference between frequency found and how strong the effects are of monogenic, oligogenic and polygenic diseaseS?

Answer 22

can generally understand whether a trait is more likely to be

monogenic: v. rare but strong effects & env effect small,

oligogenic: still rare (>0.1 to <5%). moderate effects.

polygenic common variants (>5%). weak effects. dont produce disesae in isolation. env has bigger effect