Molecular genetics Flashcards
DNA
DNA is a double stranded. Composed of many nucleotides.
Each nucleotide consists of:
A phosphate group, deoxyribose sugar, nitrogenous base (ATCG)
Each nucleotide is a base joined to a sugar phosphate unit. Two strands held by hydrogen bonds between the nitrogenous bases.
Gene: This is a portion of DNA that codes for a specific polypeptide sequence
Codon: A set of three adjacent nucleotides (triplets) each coding for an amino acid.
Exon: Polypeptide coding sequence in DNA
Intron: Non coding junk sequence
RNA
Single stranded and made up of same components of DNA
RNA contains ribose. DNA contains deoxyribose
RNA has uracil. DNA thymine
RNA much shorter than DNA
Copying DNA
Replication - New DNA copies produced from template of DNA.
Transcription - synthesis of RNA from nuclear DNA which occurs within the cells nucleus.
RNA synthesis during transcription contains introns, which do not code for polypeptides. This unprepared RNA undergoes splicing to remove the introns and become mRNA.
Transfer RNA is also synthesised from DNA
mRNA leaves the cell nucleus and enters the cytoplasm to direct protein synthesis.
Translation - refers to the process of translating the mRNA sequences into polypeptide chains. In the cell cytoplasm ribosomes read the sequence of mRNA in groups of three bases to assemble a protein. Termination occurs when stop codon read
DNA mutrations
Point mutation refer to single base alteration.
1) Silent mutation - altered codon codes for the same aa (no affect).
2) Missense mutation - Altered codon codes for a different AA
3) Nonsense - Altered codon codes for a stop signal.
Frameshift mutation - Deletion or insertion is not in multiples of three codons. Creates a shift in the way triplets are read and can have significant effects
In frame mutation - Deletion or insertion happens in multiples of three codons with no disturbance in the actual reading frame.
Translocation
Translocation refers to the exchange of genetic material in which a chromosome breaks and a portion of it reattaches to a different chromosome.
They are mostly reciprocal, so one segment is swapped for another.
Robertsonian translocation - Unequal exchange of genetic material. Results in a single fused chromosome.
Chrosomes typically involve acrocentric chromosomes (very small p arms). Two p arms are discarded and a metacentric chromosome is produced with only a small loss of genetic material.
Robertsonian translocations are considered to be balanced and viable
However when a gamete is formed only one gamete will receiving the new metacentric chrosome. One of the mechanisms for Down syndrome.
Mendelian inheritance
4 types. Autosomal dominant
Dominant conditions are expressed in individuals who just have one copy of the mutant allele.
One normal copy of the gene and one mutant copy, so each offspring has a 50% chance of inheriting the mutant copy
Exampels: Marfans, Huntingtons, NF,
AR: Recessive conditions are expressed when an individual has two copies of the mutaint allele.
Examples; Wilsons disease, homocystinuria, phenylketonuria.
X linked genetics: The mutated gene lies on the X chromosome. Means all males are affected.
X linked dominant. Conditions are rare. X chromosome must contain a disease causing mutation. Vit D resistant rickets.
Females twice as likely to be affected as they inherit two X chromosomes. If the affected male mates with a homozygous female, then all of the daughters will be affected but none of the sons.
Rett syndrome: X linked and typically only present in females.
Fragile X: X linked dominant disorder.
X linked recessive:
If a recessive disease causing X chromosome is passed onto male offspring. This is likely to cause a disease as there is no compensatory second X chrosome.
Skipped generations are common because affected males can produce carrier daughters.
X linked recessive disorder
Noonan syndrome, DMD, Red green blindness, Lesch-Nhan, Haemophilia A and B
Non mendelian inheritance
Mitochondrial inheritance.
All mitochondrial DNA is inherited from the mother.
Mitochondrial DNA can affect males and females.
Contains no introns so any mutations are likely to have affect.
Most common result in myopathies or neuropathies.
Trinucleotide repeats disorders - genetic disorders caused by presence of additional sets of codons repeating themselves Hallmark of these conditions: a pattern of inheritance in which successive generations are affected at progressively younger ages with increasing severity
Techniques in molecular genetics
Blotting techniques: Methods of detecting genetic material, with different techniques
Southern: Detect specific DNA sequences
Northern: Detect RNA
Western: Detect proteins
Fluorescent in situ hybridisation: Used to identify where a particular gene falls within an individual’s chromosome.
Hardy weinberg equilibrium
Both allele and genotype frequncies in a population remain constant from generation to generation, in a state of equilibrium in the absence of evolutionalry influences.
a principle stating that the genetic variation in a population will remain constant from one generation to the next in the absence of disturbing factors.
Describes ideal condition against which the effects of these influecens can be analysed.
Mutations
Gene flow
Genetric drift
Natural selecton
Mate choice
Genetic studies
Twin studies: For discreet traits, resemblance is expressed in terms of concordance traits.
Proband concordance rate: number of affected twins divided by total number of co-twins.
Allows for comparison with general population
A pairwise concordance rate is: number of number of twin pairs who both have disease divided by total number of pairs.
Schizophrenia genetics
Most commonly thought that these disorders result of multifactorial inheritance. Combination of genetic factors interacting with environmental factors.
Higher incidence of schizophrenia in first degree relatives of patients with the disease
Heritability is about 80%.
Important genes
COMT 22q11
DTNBP1 6p22
NRG1 8p12-p21
DISC 1q42
Affective disorder genetics
Bipolar disorder
Heritability is high 85-90%
MZ twins: 40-70% concordance
First degree relatives 5-10% concordance
General population 0.5-1.5%
Relatives with individuals with bipolar are also more likely to develop unipolar depression
Autism genetics
ADHD genetics
Autism
Heritability - 90%
Siblings of autism more likely to be born with autism than general population.
MZ twins concordance rate 80-92%
DZ twins 1-10%
Chrosomes 2,7,15 are important
Closely associated with Fragile X syndrome
ADHD
Heritability 70-80%
Risks higher for male relatives
Risk to first degree relatives 15-60%
Second degree 3-9%
