Mendelian inheritance

Question 1

What things are obvious in an autosomal dominant pedigree?

Answer 1

People affected in all generations
Males and females affected
All forms of transmission can be seen including male to male transmission

Question 2

What are the characteristics of an autosomal dominant condition?

Answer 2

Heterozygotes show pathology

Question 3

What is chance of a child inheriting an autosomal dominate condition if there parent has it?

Answer 3

1 in 2 or 50% chance

Question 4

What is variable expressivity in relation to autosomal dominate conditions

Answer 4

Variation in the presence and severity of clinical features

family members have different signs and symptoms of the same disease some may be severely affected others may b every mildly affected probably due to other genes modifying phenotype

Cannot predict how severely a child will experience a condition 50% chance of getting it

Question 5

Give an example of variable expressivity

Answer 5

Neurofibromatosis type 1 cafe au lait patches on the skin

vary in severity lots of benign tumours grown around nerves

Question 6

What is penetrance?

Answer 6

Penetrance is a measure of the proportion of individuals in a population who carry a specific gene and express the related trait

Question 7

What is reduced penetrance?

Answer 7

reduced penetrance is when there are no abnormal clinical features even though someone has inherited an autosomal dominate disorder

therefore it appears to have ‘skipped a generation’

thought to be due to interactions of other genes as well as interaction with environmental factors

Question 8

What is anticipation

Answer 8

In successive generations the age of onset of disease is reduced and/or the severity of the phenotype is increased

occurs due to expansion of unstable triplet repeats leading to earlier onset or more severe conditions

expansion of CAG in Huntingtons disease increases the risk of early onset

Question 9

What is age related penetrance?

Answer 9

Age related penetrance is a delay in the onset of an autosomal dominant disease –> some people may not even develop signs

BRACA1 and Huntingtons show age related penetrance the longer the time for the onset of symptoms if they arise the less likely they are to pass onto subsequent generations

Question 10

New mutations

Answer 10

Affected individual does not have affected parents, and wont have appeared anywhere in family history

Increased paternal age increases chances of mutation occur as there are many more divisions of th the germ cells to produce the sperm

Question 11

What is mosaicism

Answer 11

Genetic change occurring post fertilisation leading to two cell lines

Question 12

Somatic mosaicism

Answer 12

two different somatic cells lines can lead to single gene disorder conditions being less sever e.g. down Syndrome

Wont be passed onto offspring as not in the germ-line cells

Question 13

Gonadal mosaicism

Answer 13

two cells lines in the gonadal cells

parents themselves are not phenotypically effected by autosomal dominate condition but offspring seem to be due to presence of mutated allele in some germ-line cells

Question 14

What determines whether a condition is dominant or recessive

Answer 14

What gene it occurs it

mutations in genes coding for structural proteins and receptors –> lead to half the amount of functional product cannot function therefore have dominate condition and more extreme manifestation

Recessive conditions usually occur in genese codiong for enzymes or less essential receptors
one copy of the functional allele in heterozygotes is usually sufficient
however when two copies are present there is abolishment of the gene and then you get clinical signs as you cannot cope with no enzyme

Question 15

Autosomal recessive conditions

Answer 15

Only displayed phenotypically when individual is homozygous (carrying both copies of the forty allele)

Question 16

What are the characteristics of a autosomal recessive pedigree?

Answer 16

cant follow disease through the pedigree
Siblings tend to be affected

equal incidence in males and females

may be evidence on consanguinity parents are both blood relatives

Question 17

Why can consanguinity lead to increased probability of a autosomal recessive condition?

Answer 17

increased probability alleles for rarer genetic diseases meeting up as they share a common heritage

Question 18

How would you work out the likelihood of a woman who has had two children with one parter one with CF and then is having a child with another partner and want to know risk to the new child?

Answer 18

she must be a carrier (and her old partner)

need to figure out likelihood of new parter being a carrier
use Hardy Weinberg principle to calculate carrier frequency which is 1/22 for northern Europeans

then multiply both of these by the probability of child getting the disease if both the parents are carriers ie

1 X 1/22 X 1/4 = 1/88

Question 19

X linked recessive inheritance

Answer 19

mutation in a gene carried in the X chromosome and usually only manifests in males

Question 20

What are the common signs on a pedigree for an X linked recessive condition?

Answer 20

more than one generation affected

no direct male to male transmission affected males make all there daughters obligate carriers sons unaffected but daughters sons may then get condition known as knights move or horizontal transmission

usually only males affected

Question 21

Can females be affected

Answer 21

Yes females can be affected but more rarely due to:

may be homozygous. for two mutated alleles (effected farther and carrier mother)

Due to Skewed X inactivation

Turners syndrome only one X chromosome

Question 22

What are the outcomes of a woman carrier and normal farther having children

Answer 22

1 in 2 chance of each son the condition (if she was heterozygous) 1 in 4 in total

1 in 2 chance of each daughter being a carrier 1 in 4 in total

Question 23

How can skewed X inactivation lead to affected females in X linked recessive diseases?

Answer 23

usually equal inactivation and activation of maternal and paternal x chromosomes

but this can be skewed e.g a heterozygous female carrying the mutate allele is differentially expressed leading to some mild symptoms of the disease

Question 24

Give an example of an x linked ressecive disease that differential affects males and explain therefore why it is rare for males to pass on there mutated X chromosome to all there daughters

Answer 24

most X linked recessive diseases are fatal to males in the long run (haemophilia being a notable exception)

e.g Duchenne muscular dystrophy muscle weakness often die in teenage years

as death is common in many diseases males don’t reach reproductive age

Question 25

X linked dominant inheritance

how to spot it on a pedigree

Answer 25

Rare

High male lethality

No male to male transmission

Excess of females affected as affected males transmit trait to all of his daughters and they are directly affected as its dominant

Question 26

Give an example of an X linked dominant condition

Answer 26

Vitamin D resistant rickets

Rickets occurs even through there is an adequate intake of dietary vitamin D

Question 27

Y linked Inheritance how to spot it on a pedigree?

Give an example

Answer 27

Only Males infected
Males pass on trait to all of sons but to no daughters

H-y histocompatability antigen and genes involved in spermatogenesis

Question 28

Mitochondrial inheritance how to recognise it on a pedigree and why does it occur?

Answer 28

Mitochondrial inherited exclusively from mother sperms mitochondria much fewer and are actively expelled from oocyte

males never pass on the condition
affected females always pass on the condition to all of her offspring