Genetics Flashcards
What is a gene?
A unit of DNA that contains information that specifies the synthesis of a single polypeptide or functional RNA
Codon
3 adjacent nucleotides that code for an amino acid
How is gene expression controlled in cells?
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
How are chromosomes classified?
Size, shape
Identified by g-banding patterns in karyotyping
Features of Mendelian inheritance
Inherited or new mutation
Mutant allele or pair of mutant alleles at a single locus
Clear pattern of inheritance
High risk to relatives
Characteristics of chromosomal disorders
Loss, gain or abnormal rearrangement of one or more chromosomes in diploid cell
No clear pattern of inheritance
Low risk to relatives
Characteristics of multifactorial genetic diseases
Common
Interaction between genes and environmental factors
Low risk to relatives
Characteristics of mitochondrial disease
Mutations in the mitochondrial genome
Transmitted through maternal line
Mutations in somatic cells
Not inherited
Give rise to tumours
Non-disjunction
Chromosome or chromatids fail to separate at meiosis. Causes trisomy and monosomy. Can occur in autosomal or sex chromosomes
Common trisomies
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
Turner’s syndrome
Monosomy XO
Only monosomy which is not lethal
Failure to develop secondary sexual chatcteristics
Gonads degenerate to connective tissue at birth.
Causes of abnormal chromosome structure
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)
Mitochondrial disease syndromes
Most diseases are myopathies and neuropathies, maternal pattern of inheritance
Other abnormalities include retinal degeneration, diabetes mellitus, hearing loss
DNA Mutations
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
Autosomal dominant
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
Autosomal recessive
Individual must be homozygous for disease allele
1:4 chance of affected offspring in two carrier parents
Skips generations
Consanguineous marriages increases the risk
X-linked dominant
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.
X-linked recessive
Present in all male offspring, only present in homozygous females. 50% of girls will be carriers
Skips generations
Triplet repeat expansions
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
What is an allele?
An alternative form of a particular gene
Genotype
A set of alleles for all the genes carried by an individual
Phenotype
The expression of a given genotype in an individual
Genetic disorders
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.
Translocation
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
Role of translocations in cancer
Chromosomal translocations play a role in the development of cancer by
- 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
- bringing genes under the control of different promoters, causing inappropriate expression of that gene.
Agents that cause DNA damage
Radiation
Chemical mutagens
Viral genomes (integration)
Deamination of bases
How do DNA disorders arise? Give 3 examples
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
Factors required for Hardy-weinberg equation
Disease causd by a single allele Large population No migration Random mating Mutation rate remains constant No selection of alleles (positive or negative)
