Autosomal Recessive Inheritance

Question 1

____ is an example of an autosomal recessive trait

Answer 1

Sickle cell disease

Question 2

In sickle cell disease, the distorted red cells have a reduced survival time and this results in a severe ____ with a need for repeated blood transfusions.

Answer 2

chronic haemolytic anaemia

Question 3

T/F. In sickle cell disease, distorted red cells may also occlude vessels causing recurrent infarctions, especially of the lungs, bones and spleen.

Answer 3

True.

Question 4

The predominant haemoglobin in normal adults is ____ w/c has two ____ and two ____ polypeptide chains in each molecule.

Answer 4

haemoglobin A (HbA); α - globin; two β – globin

Question 5

Sickle - cell disease is caused by a point mutation in each ____ gene on chromosome ____ at the codon for the ____ amino acid.

Answer 5

β - globin; 11; sixth

Question 6

The resulting ____ has a substitution of ____ in place of _____. This difference causes distortion of red cells, especially at reduced oxygen tension (the basis of the ____) and also alters the electrophoretic mobility of the protein

Answer 6

haemoglobin S (HbS); valine; glutamic acid; ‘ sickling test’

Question 7

T/F. Patients with sickle cell disease have two mutant HbS gene copies (HbS/HbS), one having been inherited from each parent.

Answer 7

True. Autosomal recessive pattern

Question 8

Relatives ’ carrier status for sickle cell amenia can be determined by ____.

Answer 8

haemoglobin electrophoresis

Question 9

In marriages between two persons who are heterozygous to a autosomal recessive trait, what is the genotypic ratio for that trait?

Answer 9

one quarter homozygous normal, one quarter homozygous affected, and one half heterozygous normal

Question 10

T/F. If by chance a person with sickle - cell disease marries a heterozygote, then there will be a 1 in 2 chance on average that each child will be affected.

Answer 10

True.

Question 11

T/F. If both parents have sickle - cell disease, then only children with sickle - cell disease can be produced.

Answer 11

True.

Question 12

T/F. The majority of parents of children with sickle - cell disease are not blood relatives (consanguineous), but if they are there is an increased risk for this and other autosomal recessive disorders.

Answer 12

True.

Question 12

Family members at risk can be screened by the ____ or ____ and, where a pregnancy is at risk of homozygous sickle - cell disease, ____ may be offered.

Answer 12

sickling test; haemoglobin electrophoresis; prenatal diagnosis by DNA analysis

Question 13

In highly inbred populations, the affected person has a substantial risk of mating with a carrier, and this may result in a pedigree with apparent vertical transmission of an autosomal recessive trait a phenomenon called _____.

Answer 13

pseudodominant inheritance

Question 14

T/F. Hence, parental consanguinity, while not a prerequisite, is an important clue that a condition affecting their child is an autosomal recessive trait.

Answer 14

True.

Question 15

Sickle - cell disease affects up to ____ black Africans, who have a carrier frequency of up to about ____.

Answer 15

1 in 40; 1 in 3

Question 16

T/F. This high frequency of sickle cell carrier in black africans is believed to be due to the selective advantage of these carriers w/ regard to malarial infection.

Answer 16

True. Heterozygote advantage

Question 17

Ethnic associations may also arise from the ____ in genetically isolated populations (Table 8.3 ). Hence, the ethnic origin of a patient may be an important clue in the diagnosis of an autosomal recessive disorder.

Answer 17

founder effect

Question 18

At least ____ autosomal recessive traits are known in humans.

Answer 18

1730

Question 19

T/F. Autosomal recessive traits is associated with enzyme defect.

Answer 19

True. In about 15% of autosomal recessive traits, an enzyme defect has already been demonstrated and is to be expected in many of the remainder.

Question 20

For autosomal recessive traits, not just one but multiple different mutant alleles may occur at the locus. This is called _____.

Answer 20

multiple allelism or allelic heterogeneity

Question 21

T/F. In multiple allelism, some, but not all, of these alleles result in sufficient reduction of enzyme activity to produce disease in the homozygous state.

Answer 21

True. Hence, the recessive inheritance pattern

Question 22

Many conditions that were believed to be single genetic entities are now known to be genetically ____ i.e. to have several different genetic causes.

Answer 22

heterogeneous

Question 23

An individual who has two different mutant alleles at a locus is termed a _____.

Answer 23

compound heterozygote or genetic compound.

Question 24

T/F. Genetic heterogeneity should not be suspected if different modes of inheritance are apparent in different families or if offspring of parents who are autosomal recessive homozygotes are not invariably affected.

Answer 24

False.

Question 25

In ____, cell lines from two affected individuals are fused in vitro to determine whether heterogeneous cross - correction of the phenotype can be demonstrated.

Answer 25

complementation studies

Question 26

The similar term ____ refers specifically to the related situation in w/c a single genetic phenotype is known to result from mutations in different genes.

Answer 26

locus heterogeneity

Question 27

These diseases are known to result from a mutation in either of a number of autosomal genes (locus heterogeneous).

Answer 27

Tuberous sclerosis; polycystic kidney disease

Question 28

_____ refers to the converse correlation, where different mutations at one locus can result in different clinical conditions.

Answer 28

clinical heterogeneity. For example, different types of mutations in the same androgen receptor gene can result in either androgen insensitivity or spinal and bulbar muscular atrophy