Genetics Flashcards
Each human has how many pairs of chromosomes?
23 pairs in total 22 autosomal pairs, 1 sex-linked pair
Direction DNA chain is read?
5 Carbon — 3 Hydroxyl (strands in antiparallel fashion)
Bases in DNA vs RNA
A-T, C-G
A-U, C-G
Role of histone proteins
+ proteins that bind to negative sugar-phosphate backbone of DNA —– NUCLEOSOMES
G0 phase of the cell cycle
Most cells are resting, carrying out their normal function
G1 phase of the cell cycle
1st growth phase as chromosomes become ready to be replicated
S phase of the cell cycle
DNA replication occurs
G2 phase of the cell cycle
2nd growth phase involving proteins etc.
M phase of the cell cycle
Mitosis - mechanical separation of cell into two daughter cells Two daughter cells are identical, diploid cells
PMAT: prophase, metaphase, anaphase, telophase
Stage cytokinesis occurs in the cell cycle
Separation of cytoplasm into daughter cells - TELOPHASE
Variation occurs during meiosis by two main methods, which are?
Crossing over Independent segregation of homologous chromosomes
In meiosis, one diploid cell becomes..
Four haploid daughter cells
Sequence of bases that initiates the transcription of certain genes
Promoter
Sequence of bases that signal the beginning and end of transcription
Start and stop codons
Chemical that unwinds DNA
RNA polymerase
Sense strand is the binding strand to DNA - True/False
False - exact copy of sense strand (antisense is the binding strand)
Difference between introns vs exons
INTRONS: non coding sequences of mRNA not in final protein (spliced out)
EXONS: coding sequence of mRNA not in final protein (1-2% codes)
Examples of sequence variations between/within genes?
Single nucleotide polymorphisms (SNPs) Deletions/duplications
Changes in promotor or exon sequence
Copy number variations (CNVs) - extra or missing stretches of DNA
A polymorphism is…
A change in the genome that does not cause disease in its own right, but can predispose to a common disease
Chromosome 22 looks like a…
Teddy bear
The term used to describe a picture acting as description of persons chromosomal make up
Karyotype
A chromosome consists of…
Telomeres at each end Short arm (p) Centromere Long arm (q)
A chromosome is metacentric/acrocentric/telocentric if…
Both arms are roughly the same length
The p (short) arm is so short it is hard to observe
The centromere is located at the terminal end of the chromosome
An aneuploidy is…
An abnormal number of chromosomes Monosomy - missing chromosome from one pair Trisomy - extra chromosome in a pair
Reciprocal translocations are when…
Segments from two different chromosomes have been exchanged
Robertsonian translocations are when…
A chromosome attaches to another chromosome at the centromere Only occurs with 13, 14, 15, 21, 22 - two acrocentric chromosomes stuck end-end creating a normal phenotype
Monosomy of the sex chromosomes causes…
Turners syndrome 45XO
Trisomy of chromosome 21 causes…
Downs syndrome
What is FISH?
DNA probes specifically bind to areas of individual chromosomes and apply a fluorescein stain to make the chromosome visible Useful for detecting aneuploidies
What is Array CGH?
Genomewide search to detect polymorphisms using dye and a scanner to show abnormalities between the sample and a reference (QUANTITIES)
What is G banding?
Forces bands to appear on chromosomes using stains, helping to identify particular genetic diseases - unique pattern of bands for each chromosome
Extra chromosome 18 causes…
Edwards syndrome
Extra Y/X chromosome causes…
Klinefelters syndrome
Methods of targeted testing for small genetic changes…(2)
PCR - original DNA strand is duplicated and then copies are made increasing the mutation which is detected when compared to the trace
NGS - DNA fragmented and rebuilt using the reference to show mutations
Types of point mutations
MISSENSE single nucleotide change creates a codon that codes for a different AA
NONSENSE single nucleotide change codes for a premature stop codon
INSERTION
DELETION
Types of genetic changes (3)
MUTATION
POLYMORPHISM
VARIANT OF UNKNOWN SIGNIFICANCE
Autosomal dominant disease occurs when…
There is one faulty copy of the gene Seen in all generations 50% risk of affected child if parent affected
Autosomal recessive disease occurs when…
There are 2 faulty copies of the gene Often only one generation affected 25% risk of affected child if parents are carriers Increased likelihood if parents are related
X-linked disease occurs when…
The disease is carried on the X-chromosome
- only 50% of male children of a female carrier affected
- 50% of female children of a female carrier affected
- All male children of a male carrier normal
- All female children of a male carrier will be carriers
What is a caveat?
Female carrier shows mild features of X-linked disease
Process preventing a double dose of gene products
X INACTIVATION: one X chromosome of females randomly inactivated using XIST gene of XQ13 via METHYLATION
Methylation inhibits which process?
DNA transcription - chemic modification that does not change base sequence but interacts with histones on DNA
The term used to describe X inactivation ‘gone wrong’ is….
SKEWING: Inactivation of one X chromosome favoured over another - mutation in XIST gene - results in uneven number of cells with X chromosome inactivation
Penetrance is defined as…
The likelihood of having the disease given you have the genetic mutation
Mendelian inheritance encompasses which disorders?
Autosomal dominant
Autosomal recessive
X-linked
Mitochondrial
Penetrance in…
a) Mendelian disorder
b) Multifactorial disease
a) High - controlled by mutation in single gene with a small environmental input
b) Low - genetic change attributed to environmental input
Common disease - common variant hypothesis
Common disease causing variants will be found in all human populations which show a disease but not necessarily expressed in phenotype
What is imprinting? What is it controlled by?
Variation in gene expression depending on which parent you inherit the gene from e.g. in Angelman’s syndrome, mother’s UBE3A works fine but father’s is methylated - controlled by methylation
Mitochondrial disease occurs when…
Diseased mitochondria passed from mother to child
Heteroplasmy is when
Different daughter cells contain different proportions of mutant mitochondria (similar to mosaicism)
What is mosaicism?
Occurs when cells within the same person have a different genetic makeup (causes cancer)
Epigenetic variation describes…
Functional modifications to the genome that do not involve a change in the nucleotide sequence
Where are the 2 checkpoints in the cell cycle where DNA can acquire mutations?
Between G2 and M Between G1 and S
What is the function of oncogenes?
Promote cell division
What is the function of tumour suppressors?
Inhibit cell division
Only one copy of the tumour suppressor gene is required to be mutated for cancer to occur. True/False?
False 2 copies required (2 Hit Hypothesis)
Cancer is most often inherited as a high penetrance Mendelian disorder. True/False?
False More usually multifactorial
Risk of breast cancer:
a) High
b) Medium
c) Low (population risk)
a) BRCA1 mutation
b) mother/sister breast cancer at 45
c) mother with breast cancer at 70
