Intro And Modes Of Inheritance

Question 1

How many chromosome and genes do we have?

Answer 1

46 (23 pairs)
25000 genes

22 aoutosomal pairs and one pair of sex chromosomes
Male: XY
Female: XX

Question 2

What is mitochondrial DNA?

Answer 2

Around 16500 base pairs
Codes for 15 proteins, rRNA and tRNA

All derived from mother

But most mitochondrial proteins are encoded by the cell genome

Question 3

What are different versions of a gene called?

Answer 3

Alleles

Question 4

What are Hetero and homozygous?

Answer 4

Heterozygous
Two different alleles

Homozygous
Two identical alleles

Question 5

What is the position of a gene called?

Answer 5

Locus

Question 6

What are three types of human genetic disorder?

Answer 6

Single gene disorders

Chromosomal disorders

Complex disorders

Question 7

What are single gene disorders?

Answer 7

Most common genetic disorders effect (1/500) people But there are >5500 types

But overall they affect a large number of people (1.5%)

Affect all body systems so concern all specialities

Large health burden

Question 8

What are chromosomal disorders?

Answer 8

Affect 1/150 live births

Occur when a chromosome is damaged during formation of sperm or egg or during early development of the embryo

Question 9

What are complex disorders?

Answer 9

Common diseases

Result of genetic and environmental factors

E.g obesity and type II diabetes

Question 10

What do autosomal dominant diseases mean?

Answer 10

A characteristic is dominant if it manifests in a heterozygote

Refers to phenotype

Single gene disorders

Affects multiple generations

Us usually one affected parent at least

1/2 chance of being affected

Males and females affected equally

Vertical pedigree pattern

Question 11

Why are some genes dominant? (Simple)

Answer 11

Certain alleles activate genes, others leave them inactivate

E.g. eye colour
Gene responsible is OCA-2

Active —> melanin —> brown
Inactive —> no melanin —> blue

Therefore an allele that causes OCA-2 to be active overrides the lack of melanin

Question 12

What are the three ways in which a single gene disorder is dominant?

Answer 12

Gain-of-function

Dominant negative effect

Insufficient

Question 13

What does gain of function mean?

Answer 13

A gene now makes a protein with a new function
Which isn’t usually seen
E.g. longer lifespan of protein or new location

Question 14

What does a negative dominant affect mean?

Answer 14

The mutated form interferes with the activity of proteins it binds

E.g. in dimers or multimers which reduces activity of other proteins in the multimer

Question 15

What does insufficiency mean?

Answer 15

Mutant in one gene results in 1/2 the amount of a protein

This is not a sufficient amount for normal function

Question 16

What is a carrier of a disease?

Answer 16

Only in autosomal recessive

Lost a single copy of a gene but the remaining one is sufficient for normal function

Question 17

What are some properties of autosomal recessive disorders?

Answer 17

Parent and children normally unaffected

One or more siblings affected

1/4 chance of being affected (two carrier parents)

Males and females equally affected

Horizontal pedigree pattern

Question 18

What do consanguineous marriages mean in terms of autosomal recessive disorders?

Answer 18

Elevate the risks of these diseases
1/5 of the wotrlds preference for marriage includes this
Rarer diseases with a lower gene frequency have a much higher relative risk

Disease gene frequency (q) 0.01 0.001
Relative risk in 1st cousins 6.25 62.5

Question 19

How do autosomal recessive dosorders cause loss of function?

Answer 19

Work less well
Degraded faster
Inadequate amounts

Question 20

What are the sex chromosomes?

Answer 20

X
1000-1300 genes

Y
150 genes

Men: XY
Women: XX

Question 21

What are some points about X linked recessive disorders?

Answer 21

Affect mainly males (essentially dominant)

Affected boys may have affected uncles

Parents and children are commonly unaffected

Children of a man with one: boys will be healthy, girls will all be carriers

I’m some cases female characters can exhibit subtle signs

Question 22

What are some properties of x linked dominant diseases?

Answer 22

Similar pattern to autosomal dominant

But: all daughter but no sons of a an affected father are affected

All children of an affected mother can be affected

Often milder conditions in females than males due to random x inactivation

Some males affected by these diseases are not viable so these diseases are only present in females

Question 23

What are some features of y linked disorders?

Answer 23

Only affect males 
Very rare 
All sons of a father are affected 
Vertical pedigree pattern 
So few diseases because of limited number of genes in the Y chromosome

Question 24

How are mitochondria inherited in humans?

Answer 24

From the mother

So all diseases caused by mutations in mitochondrial DNA are maternally inherited

Vertical pedigree pattern

All children of an affected mum
Will be affected
None from an affected dad

However all mitochondrial diseases are very variable within a family

Question 25

Why do mitochondrial diseases show so much variability in expression?

Answer 25

Heteroplasmy - mitochondria have several copies of genome, not all are mutated
They only express the disease above a threshold
Mutated genes can be gained or lost in binary fission

Random segregation during cell division, different numbers of diseases mitochondria will be passed into daughter cells
Must reach a threshold to develop symptoms

Most mitochondrial diseases develop with age due to accumulation of mutant mitochondria