Genetics

Question 1

What is a gene?

Answer 1

A unit of DNA that contains information that specifies the synthesis of a single polypeptide or functional RNA

Question 2

Codon

Answer 2

3 adjacent nucleotides that code for an amino acid

Question 3

How is gene expression controlled in cells?

Answer 3

Chromatin structure: DNA tightly bound to his tones and packaged as chromatin, affects binding of transcription factors and RNApol

Epigenetic control: change in pattern of gene expression by altering DNA/chromosome structure e.g. DNA methylation

Transcriptional initiation: controlled by promoters and DNA binding proteins

Question 4

How are chromosomes classified?

Answer 4

Size, shape

Identified by g-banding patterns in karyotyping

Question 5

Features of Mendelian inheritance

Answer 5

Inherited or new mutation
Mutant allele or pair of mutant alleles at a single locus
Clear pattern of inheritance
High risk to relatives

Question 6

Characteristics of chromosomal disorders

Answer 6

Loss, gain or abnormal rearrangement of one or more chromosomes in diploid cell
No clear pattern of inheritance
Low risk to relatives

Question 7

Characteristics of multifactorial genetic diseases

Answer 7

Common
Interaction between genes and environmental factors
Low risk to relatives

Question 8

Characteristics of mitochondrial disease

Answer 8

Mutations in the mitochondrial genome

Transmitted through maternal line

Question 9

Mutations in somatic cells

Answer 9

Not inherited

Give rise to tumours

Question 10

Non-disjunction

Answer 10

Chromosome or chromatids fail to separate at meiosis. Causes trisomy and monosomy. Can occur in autosomal or sex chromosomes

Question 11

Common trisomies

Answer 11

13- Patau syndrome ( die within hrs/days)

18- (die within weeks of birth)

21- Down’s syndrome, mental retardation, stunted growth

XXY- kleinfelters, mild learning difficulty, infertility

XXX- triploX syndrome, mild mental retardation

XYY- Jacobs syndrome, usually asymptomatic

Question 12

Turner’s syndrome

Answer 12

Monosomy XO
Only monosomy which is not lethal
Failure to develop secondary sexual chatcteristics
Gonads degenerate to connective tissue at birth.

Question 13

Causes of abnormal chromosome structure

Answer 13

Deletions (prader-Willi/angleman syndrome caused by deletion in 15q)

Duplications (Charcot-Marie-tooth disease caused by duplication in ch17)

Inversion (end to end reversal of segment within a chromosome)

Translocations (two chromosome regions join together, Down’s syndrome)

Question 14

Mitochondrial disease syndromes

Answer 14

Most diseases are myopathies and neuropathies, maternal pattern of inheritance
Other abnormalities include retinal degeneration, diabetes mellitus, hearing loss

Question 15

DNA Mutations

Answer 15

Mis-sense: substitution of one base for another
Insertion/deletion: shifts reading frame
Splicing mutations: abnormal spicing of mRNA to include intron sequences
Non-sense: premature stop codon
Duplication
Translocation

Question 16

Autosomal dominant

Answer 16

One copy of mutant gene sufficient to cause disease
Passed equally from male to female
Present in each generation

Problems with detection:
Incomplete penetrance
Variable expression (mildly affected parent has severely affected child)
New mutation

Question 17

Autosomal recessive

Answer 17

Individual must be homozygous for disease allele
1:4 chance of affected offspring in two carrier parents
Skips generations
Consanguineous marriages increases the risk

Question 18

X-linked dominant

Answer 18

Affects heterozygous females and all male offspring

Passed equally to male and female from affected mother, all females off affected father will have the disease.

Question 19

X-linked recessive

Answer 19

Present in all male offspring, only present in homozygous females. 50% of girls will be carriers
Skips generations

Question 20

Triplet repeat expansions

Answer 20

Caused by stalling of the DNA polymerase during replication in areas of polyglutamine tracts (CAG rich) resulting in multiple repeats. The severity of the disease is related to the number of repeats.

Some diseases show gene anticipation, the number of repeats expand with each generation, can cause earlier onset of symptoms.

e.g. Huntingtons, Fragile X syndrome

Question 21

What is an allele?

Answer 21

An alternative form of a particular gene

Question 22

Genotype

Answer 22

A set of alleles for all the genes carried by an individual

Question 23

Phenotype

Answer 23

The expression of a given genotype in an individual

Question 24

Genetic disorders

Answer 24

Due to defects in an individuals DNA

Can be chromosomal (change in number or chromosomal rearrangements) which leads to a loss or gain of genetic material; or due to changes in the base sequence of the DNA which normally leads to a change in the protein and a change in cell behaviour.

Question 25

Translocation

Answer 25

Occurs when a segment of a chromosome moves to another position in the genome. This is usually reciprocal and can cause deletions or duplications within the DNA. e.g. Cri-du-chat

Question 26

Role of translocations in cancer

Answer 26

Chromosomal translocations play a role in the development of cancer by

1. causing two genes to fuse together, producing a hybrid gene encoding a chimeric protein with a distinct, constitutive activity. e.g. bcr-abl gene in CML caused by translocation of Ch9 and Ch22
2. bringing genes under the control of different promoters, causing inappropriate expression of that gene.

Question 27

Agents that cause DNA damage

Answer 27

Radiation
Chemical mutagens
Viral genomes (integration)
Deamination of bases

Question 28

How do DNA disorders arise? Give 3 examples

Answer 28

DNA disorders are mostly spontaneous point mutations that arise due to errors in DNA replication which are not detected by DNA repair systems. This can result in substitutions, deletions, insertions or inversions of the DNA. This can affect the activity of the resulting proteins.

e.g.
Sickle cell anaemia: A>T mutation
Musculat dystrophy: insertion of a base in the dystrophin gene
Cystic fibrosis: deletion of a triplet codon F508

Question 29

Factors required for Hardy-weinberg equation

Answer 29

Disease causd by a single allele
Large population
No migration 
Random mating
Mutation rate remains constant
No selection of alleles (positive or negative)