Study Unit 3

Question 1

Define polyploidy

Answer 1

The condition in which a normally diploid cell or organism acquires one or more additional sets of chromosome.
Example: triploidy = one extra 3n=69XXY
Tetraploidy= two extra sets 4=92XXXX

Question 2

Define Aneuploidy

Answer 2

1. Addition or loss of one chromosome
   Example: trisomy, 47XY+21
   Monosomy 45X

Question 3

Define Mixoploidy

Answer 3

An organism having different numbers of chromosomes in different cells

Question 4

Define Euploidy

Answer 4

Complete set of chromosome, no gain, no loss 2n=46

Question 5

Origin of triploidy

Answer 5

1, dispermy (most common) two sperm fertilising a single egg.
2. Diploid gametes: diploid sperm or ovum

Question 6

Meiotic non-disjunction

Answer 6

Process in which paired chromosome fail to separate during meiotic anaphase 1 and migrate to the same daughter cell, or sister chromatids fail to disjoin at either meiosis 2 or mitosis.

Question 7

What causes tetraploidy (polyploidy)

Answer 7

This happens when a normal zygote that undergo normal DNA duplication but no cell division (endomitosis)

Question 8

non-disjunction during meiosis results in.

Answer 8

1. Results in Gametes with 22 or 24 chromosome resulting in a trisomic or monosomic zygote.

Question 9

Results of non disjunction during mitosis.

Answer 9

Results in autosomal cells that are mosaic mix of normal and aneuploid cells.

Question 10

What is the anaphase lag

Answer 10

Chromosome or chromatid delayed in movement during anaphase-lags behind-may fail to incorporate into daughter cell nucleus.

Question 11

Mosaic vs chimera

Answer 11

Mosaic: results from two or more genetically different cell lineage as a result of mitotic non-disjunction.
Chimera: is a result of fusing of two genetically distinct fertilised eggs.

Question 12

Explain balanced structural chromosomal abnormalities

Answer 12

1. No change in amount of genetic material
2. Cause by inversion and translocation

Question 13

Explain unbalanced structural chromosomal abnormalities

Answer 13

1. Gain or loss of essential chromosome segments
2. Caused by deletions, duplication, insertions and rings and isochromosomes

Question 14

Explain what an inversion is and what two types of inventions do you get.

Answer 14

1. Inversion: rearrangement in which an internal segment of a chromosome has been broken twice, flipped 180 degrees and re-joined.
2. Paracentric inversion: 2 breaks in same arm
3. Peri centric inversion: breaks in different arms

Question 15

What can happen after incorrect repair of two breaks on a single chromosome.

Answer 15

1.interstitial deletions
2. Paracentric inversion
3. Peri centric inversion
4. Ring chromosome

Question 16

What the centromere dictates about propagation of structurally abnormal chromosome.

Answer 16

structurally abnormal chromosome with a single centromere can be stably propagated through successive rounds of mitosis. However, any repaired chromosome that lacks a centromere or posses two centromeres will normally not segregate stably at mitosis, and will eventually be lost.

Question 17

Explain 4 isochromosome

Answer 17

1. This is the loss of one arm with duplication of the other.
2. Either p OR q arm lost a possible explanation centromere divided transversely.
3. The most common isochromosome is when the two long arms of X-chromosome

Question 18

Loss of function and gain of function in recessive disorder.

Answer 18

1. Mutant allele in recessive disorders cannot be a gain of function.
2. Loss of function + normal allele= normal phenotype.
3. Loss of function + loss of function = Disease phenotype

Question 19

When can loss of function mutation in the heterozygote state be dominant.

Answer 19

When there are haplo-insufficiency: 50% of normal function not sufficient for normal genotype.
Or
Imprinting gene : in certain allele sets, only one allele is transcribed the other parental allele is being silence.
Or
Dominant-negative mutation in genes that transcribe parts of A dimer or multimers.

Question 20

Explain Loss-of-function in a dominant disorder in dosage sensitive genes.

Answer 20

1. Dosage sensitive genes: the amount of product that is made is critically important . Often these products have roles in quantitative signaling system or other situations in which precisely defined ratios of the products of different genes are important for them to work together effectively.

Question 21

Explain how dominant-negative mutation causes autosomal dominant disorders.

Answer 21

This is when the product of the mutant allele results in a mutant protein that cannot perform the function of the normal protein and also inhibit the function of wild-type protein produced by the normal allele. Common in proteins which are dimers or multimers.

Question 22

What is an example of of an autosomal dominant disorder caused by dominant -negative mutations.

Answer 22

1. Osteogenesis imperfecta
2. Osteogenesis imperfecta caused by defects in formation of bone also called brittle bone disease.
3. Cause by defects in type 1 collagen

Question 23

What are the four types of osteogenesis imperfecta

Answer 23

1. Types I and V less severe bone fragility
   2.types 2 and 3 severe bone fragility, with type 2 being the most severe form.

Question 24

Explained how osteogenesis imperfecta type 1 is cause by dominant negative mutations.

Answer 24

Two COL1A1-encoded polypeptides and one COL1A2-encoded polypeptide are required to make a triple -helical type 1 pro-collagen.. A null allele at COL1A1 simply reduces the amount of type 1 pro-collagen by half and results in a mild form of Osteogenesis.

Question 25

Explained how osteogenesis imperfecta type 2 is cause by dominant negative mutations.

Answer 25

mutations that replace a structurally important glycine with any other amino acid usually have strong dominant effects because the disrupt the packing of the three chains in the triple helix . The mutant COL1A1-encoded polypeptide is included within three-quarters of the type 1 procollagen molecules made, making them nonfunctional.

Question 26

Clinical features of osteogenesis imperfecta type 1

Answer 26

1. Mild bone fragility
   ‘2. Blue sclerae (white outer coat of the eye) which is caused by conjunctiva becoming thinner and transparent which means refracted light shifts towards blue.
2. Hearing loss in 50% of the patients due to faulty formation of auditory ossicle
3. Normal stature and few bone deformities.

Question 27

Clinical features of osteogenesis imperfecta type 2

Answer 27

1. Extreme bone fragility
2. Long bone deformities like compressed femurs.
3. Lethal in perinatal period most die of respiratory failure.

Question 28

Types of mutation that cause type 1 osteogenesis imperfecta. (No protein)

Answer 28

1. Nonsense
2. Frameshift
3. Defective mRNA synthesis

Question 29

Types of mutation that cause type 2 osteogenesis imperfecta. (No protein)

Answer 29

1. Missense

Question 30

Gain of function mutations is dominant disorders caused by

Answer 30

1. Increased protein activity (enhanced normal function of a protein)
2. Increased gene dosage (>3 copies of gene) ,excess of protein leading to disease phenotype.

Question 31

Define null allele

Answer 31

Allele produce no product

Question 32

Define hypomorph

Answer 32

Allele produce reduce amount of product/activity .

Question 33

Define hypermorph

Answer 33

Allele produce increased amount of product/activity

Question 34

Define neomorph

Answer 34

Allele with novel activity/product

Question 35

Define Allele heterogeneity

Answer 35

Mutations in the same gene can be responsible for more than one disorder.

Question 36

What is an example of allelic heterogeneity gene.

Answer 36

receptor tyrosine kinase gene

Question 37

Mutation in the receptor tyrosine kinase molecule results in.

Answer 37

1. Hirschprung disease
2. Familial medullary thyroid carcinoma,
3. Multiple endocrine neoplasia type 2

Question 38

Explain hirschprung disease

Answer 38

1. Characterised by missing nerve cells in the colon muscle.
2. caused by a nonsense and Frameshift mutation that causes a loss of function .
3. Results in autosomal dominant disorder.

Question 39

Explain familial medullary thyroid carcinoma

Answer 39

1. caused by activating missense mutation which leads to a gain of function in the N-terminus and transmembrane domain.
2. Causes an autosomal dominant disorder.

Question 40

Explain multiple endocrine neoplasia type 2

Answer 40

1. caused by activating missense mutation which leads to a gain of function in a autosomal dominant disorder
2. MEN2A= MTC parathyroid hyperplasia and phechromocytoma
   3.MEN2B= same as MEN2A, but without parathyroid hyperplasia.

Question 41

Explain locus heterogeneity

Answer 41

1. A disease than can be caused by mutations at different loci.
2. Thus the association of more than one locus with a specific clinical condition

Question 42

Explain how Bardet-biedl syndrome (BBS)

Answer 42

1. Affects 15 loci responsible for cilia function.
2. It is a Pleiotropic disorder which means many different body system are impaired.

Question 43

Define the locus heterogeneity disorder sensorineural deafness.

Answer 43

1. Caused by mutations in 28 different genes.
2. Autosomal recessive
3. Child with two affected can be phenotypically normal

Question 44

Double heterozygous

Answer 44

A child is heterozygous for two different mutant alleles that cause the same disease.

Question 45

How can a child who has two homozygous recessive parents for sensorineural deafness.

Answer 45

Sensorineural deafness is a locus heterogeneity disorder: meaning mutations on multiple alleles can cause the same disorder. Therefore the parents are mutant on different alleles meaning the child will be double heterozygous for the mutant alleles.

Question 46

What is genomic imprinting

Answer 46

This is when some genes are expressed only from maternal or paternal copy, therefore there is unequal expression of some genes.

Question 47

What happens to a Imprinted gene to inactivate it.

Answer 47

The gene is methylated

Question 48

How does imprinting affect disease phenotype.

Answer 48

1. If active allele is mutated = disease phenotype
2. If silenced allele is mutated = normal phenotype

Question 49

Characterise angelman syndrome

Answer 49

1. Paternal imprinting =Deletion of maternal chromosome 15q11( account for 70% of cases)
2. Both copies of chromosome 15 from father ( account for 5% of cases)
3. Key disease locus UBE3A

Question 50

What are imprinting disorders

Answer 50

1. Functional gene copy number reduced to zero.
2. Deletion of the only functional copy

Question 51

Characterise prayer-willi syndrome

Answer 51

1. Maternal imprinting = Deletion of paternal chromosome 15q11 (account of 70% of cases)
   2.both copies of chromosome 15 from mother ( account of 25% of cases)
2. Key disease locus SNORD116

Question 52

Explain what uniparental disomy is.

Answer 52

1. Both copies of specific chromosome pair derived from one parent.
   2 types:
   - heterodisomy: both homology from one parent.
   - isodisomy: one chromosome in duplication

Question 53

Origins of uniparental disomy

Answer 53

1. Trisomy not compatible with life may be rescued: loss of one copy of trisomic chromosome by chance lost chromosome may be only copy originating from one parent.
   OR
2. Monosomy not compatible with life “rescued” the chromosome is duplicated.