Lecture 1 - basic human genetics Flashcards
Describe the human genome
23 pairs chromosomes
22 pairs of autosomes
1 pair of sex chromosomes (gametes)
What is an allele?
Variants of a gene (dominant and recessive)
What is a genotype?
Unique combination of alleles in an individual
What is a phenotype?
Observable trait/ characteristic (genotype + environment)
Describe the structure of DNA
2 strands of DNA coiled around (double helix). Each strand is a nucleotide containing phosphate, sugar, and bases (ACTG)
What does the helicase enzyme do?
First stage of replication, unzips the 2 strands of DNA creating a replication fork
What does the enzyme primase do?
Makes primer
What does the primer do in replication process?
Marks start of new DNA, it is a small piece of RNA
What does DNA polymerase do?
Binds to the primer during replication, adds DNA bases to create DNA
In what direction can bases be added in replication?
5’ to 3’
Which strand of DNA is made continuously during replication by DNA polymerase?
The leading strand
What are the small chunks of DNA on the lagging strand called?
Okazaki fragments
What does the enzyme exonuclease do?
removes all the RNA primers, then another polymerase fills in these gaps
What happens after exonuclease has removed the RNA primers?
DNA ligase seals up DNA strands
Why is replication described as a semi-conservative process?
Each new DNA is made up of one new strand, and one old conserved strand
Where is the genome?
The nucleus
What does RNA polymerase do?
Attaches to a gene when it is turned on, makes strand of mRNA out of free bases in the nucleus (order determined by DNA code)
Describe translation process
mRNA moves into cytoplasm and binds to ribosomes. Chain of amino acid created from mRNA which is read 3 bases at a time (triplet). Transfer RNA carries amino acid chain to ribosomes
What % of DNA codes for proteins?
2%
What is 98% of DNA called and what does it do?
Non-coding DNA, serves purpose in gene expression (on/off)
What are exons and introns?
Exons are protein coding DNA, introns regulate gene expression
What is a transcription factor?
Regulates whether gene is transcribed or not (control mRNA transcription), when transcription factor binds to regulatory sequence, the gene is freed for transcription
What are homeobox genes?
Control timing of developmental body parts/ anatomical development
How many base pairs account for individual differences?
About 1 in 1000 base pairs, most DNA is shared
What is a common gene variant?
About 2 million base pairs differ in at least 1% of the population
What is a rare gene variant?
When base pairs differ in less than 1% of the population
What is a somatic mutation and what can it cause?
A mutation in somatic cells (not egg or sperm cells) - this can cause cancer
What is a polymorphism?
Mutations resulting in new alleles that cause heritable genetic variation (gametes)
What is a single nucleotide polymorphism?
Most common DNA polymorphism, has just 2 gene variants
What is a synonymous SNP?
A change in the DNA has occurred, but it still codes for the same amino acid
What is a non synonymous SNP?
A change in the DNA causes a change in the amino acid sequence - causes different structure/ protein which will have a different function
What is a nonsense mutation?
When the mutation which has changed the base pairs results in the production of a stop codon creating truncated protein
Is a nonsense mutation synonymous or a non synonymous SNP?
Non synonymous
What is a missense mutation?
Mutation resulting in amino acid change
Is nonsense or missense more severe?
Nonsense usually more severe effects
What is a triplet repeat mutation?
Multiple repeats of 3 nucleotides, when these become very long it can result in disease/ disorder
What is Huntington’s caused by?
Triplet repeat of ‘CAG’ (normal to have 11 to 34 triplets. HD has 40 to 100 repeats)
What does the ‘CAG’ code for (Huntington’s)
Codes for glutamine, in longer chain mutation this is toxic to nerve cells (HD gene switched on in nerve cells)
What causes fragile X syndrome?
Expanded triplet repeat of CGG on X chromosome near the end - long repeat cause fragile X chromosome
Describe what a long sequence of CGG means for fragile X syndrome
Normal to have 6 to 54 repeats. Longer repeat of 200 is still a normal phenotype, but means offspring will have 200+ repeats
What is the FMR1 gene?
In full mutation of fragile X syndrome, FMR1 gene is blocked so FMR1 protein not coded for. Protein thought to have role in establishing connections between brain cells making them more efficient
Why is fragile X more common in men than women?
Women (XX) have 1 inactivated X chromosome (DNA of only one of them is transcribed) - mutation may be active in some cells but not others leading to more variable symptoms
What is a copy number variation?
When large regions of the genome are deleted or duplicated resulting in either more or less protein synthesis (function changes)
What is a de novo mutation?
When a mutation is not inherited from parents
When are de novo CNVs more common?
More common in simplex families (1 affected individual) than multiplex families (multiple affected individuals)
What is a gross alteration to the chromosome?
Change in the number of chromosomes due to nondisjunction
What is nondisjunction?
During meiosis, each chromosome duplicates to form sister chromatids - nondisjunction is the failure of these chromatids to separate properly (most disjunction is lethal)
What is trisomy 21?
Down syndrome, extra chromosome number 21
Why are older mothers more likely to have children with down syndrome?
In females, meiotic cell division begins before birth, is halted until puberty begins, and then continues until menopause. Production of egg just before menopause has been halted for many years so more likely for nondisjunction
What is Mendel’s first law of heredity?
Law of segregation - the two members of a pair of alleles separate during gamete formation. Consequently, each gamete contains only one member of every pair of genes
What is the Hardy-Weinburg equilibrium?
allelic and genotypic frequencies remain the same, generation after generation, in the absence of forces such as natural selection that change these frequencies
What is the frequency of offspring genotypes in Hardy-Weinburg equilibrium?
p2 + 2pq + q2
What is Mendel’s second law?
Inheritance of one gene is not affected by inheritance of another gene
What violates Mendel’s second law?
Linkages - loci close together on the chromosome (more probability of recombination). De novo mutations also violate this law as there is no heritable aspect.
What is a regulation factor?
A substance in the environment that switches off the inhibition of transcription (regulatory DNA) so it can be transcribed (turned on)
What is the implication of the X chromosome being larger than the Y
Means that some genes on a males X chromosome will have no equivalent genes on Y, resulting in recessive X-linked genes being expressed (no counteracting dominant genes)
What is PKU caused by?
Recessive allele that fails to produce enzyme necessary to metabolise the protein phenylalanine present in milk - builds up and becomes toxic
