AUTOSOMAL RECESSIVE

Question 1

Autosomes (22 pairs):

Answer 1

two
of every autosome therefore
two copies of each
autosomal gene

Question 2

An autosomal recessive trait is that

which manifests in the

Answer 2

homozygous state,
that is, in
a person possessing both copies
of abnormal/ mutant allele

Question 3

HOW ARE THEY PASSED ON?

Answer 3

There are two copies of every
autosomal gene
Both copies of the gene function to
produce a product (i.e. protein)
One copy of each gene is passed to a
child from parents
2 mutant copies = disease
manifestation

Question 4

CARRIERS

Answer 4

The disease only manifest when 2 copies are mutated
Heterozygous individuals are said to be genetic carriers of the mutation for that
condition
Protein is halved but adequate
One gene mutation does not usually cause a health condition

Question 5

obligate carrier

Answer 5

An obligate carrier is an individual who may be
clinically unaffected but who must carry a gene
mutation based on analysis of the family history

Question 6

ALLELIC

HETEROGENEITY

Answer 6

For some recessive conditions
1 specific mutation gives rise to
the phenotype (e.g. sickle cell
anemia)

For other disorders, it is possible
that, many different mutations
within the same gene, can arise
and will result in the same genetic
condition (e.g. cystic fibrosis

Question 7

cystic fibrosis

Answer 7

there are currently 2088 mutations listed in the CFTR mutation database

Question 8

EFFECTS OF ALLELIC HETEROGENEITY

Answer 8

1. Can result in clinical
variability depending on how
the specific mutation disrupts
the gene’s structure and/or
function

2. Disease severity is determined
   according to the position of
   the mutation is coding or non-coding

Question 9

noncoding mutation

Answer 9

missense, nonsense, silent, frameshift

Question 10

coding mutation

Answer 10

splice site, regulatory

Question 11

COMPLICATIONS TO GENETIC TESTING OF ALLELLIC HETEROGENIC MUTATION

Answer 11

• Makes mutation analysis difficult, where to start looking in the gene?
• Population genetic information is therefore essential
• Allows screening of the most common mutations (cost/benefit)
• Common CFTR mutations in South Africa:
• c.2988+1G>A - African population
• p.Phe508del - Caucasian population

Question 12

COMPOUND

HETEROZYGOSITY

Answer 12

In medical genetics, compound heterozygosity is the condition of having two or more heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state; that is, an organism is a compound heterozygote when it has two recessive alleles for the same gene, but with those two alleles being different from each other

Question 13

COMPOUND

HETEROZYGOSITY explanation

Answer 13

­ The exact same deleterious mutation is unlikely to happen
repeatedly at the exact same place in a gene
­ BUT: If both are loss of function alleles à clinical effect is
the same as a homozygote
­ Most individuals with the recessive disease are compound
heterozygotes

Question 14

CONSANGUINITY

Answer 14

Increase the chance that two individuals will be carriers of the same mutant allele

Cousin marriages are legal/ acceptable in many cultures/ religions/ populations

Rare alleles are more likely to “meet up” in the offspring of cousins than in the
offspring of parents who are unrelated

General population risk of having a child with a birth defect: 2-3%

1st cousin marriages: 5-6% risk

Question 15

g

Answer 15

mutant genotype

Question 16

G

Answer 16

normal genotype

Question 17

gg

Answer 17

affected

Question 18

GG/Gg

Answer 18

unaffected

Question 19

The outcomes for each pregnancy are the same whether it is the mother who is affected or the father

Answer 19

true

Question 20

Parents of affected
individuals (carriers) are
usually phenotypically
normal

Answer 20

true

Question 21

Affected individuals are
NOT seen in every
generation

Answer 21

true

Question 22

Male to female and female
to male transmission
&
Men and women are equally
affected

Answer 22

true

Question 23

Examples of recessive disorders:

Answer 23

1. Cystic fibrosis (CF)
2. Sickle cell anemia
3. Oculocutaneous albinism (OCA)
4. Haemochromatosis
5. Tay Sachs disease

Question 24

Both copies of the genes must be mutated to express the condition

Answer 24

true

Question 25

Different individuals may be a different mutation within the same gene but produce
the same phenotype

Answer 25

true

Question 26

The phenotype may manifest as a result of a single individual having two different
mutations within the same gene

Answer 26

true

Question 27

§ If a child is affected both parents are carriers (obligate)

Answer 27

true

Question 28

Carrier individuals do not express the condition

Answer 28

true

Question 29

With each pregnancy, an affected individual has a 100% chance of passing on
the mutant allele to their offspring

Answer 29

true