Genetics - Genetic Inheritance Flashcards
In which direction is DNA replicated and read?
5’ to 3’ direction
What forms the backbone of DNA?
2-deoxyribose
What forms the backbone of RNA?
ribose
What are the bases in DNA?
ACGT
What are the bases in RNA?
ACGU
How do the bases pair in DNA?
A - T
G - C
What is a chromosome?
DNA stand wound with histones
How can damage during replication cause disease?
DNA can be damaged during replication
Usually fixed by repair mechanisms
Defects in repair mechanism cause disease
What is mitosis?
Division of diploid parent cell into two identical diploid daughter cells
What is meiosis?
Division of one diploid parent cell into 4 heterogenous haploid daughter cells
Describe meosis.
DNA replication and recombination
First round of division into two diploid cells
Second round of division into 4 haploid cells
Recombination introduced genetic variation
What is the difference in structure between RNA and DNA?
DNA = double stranded
RNA = single stranded
What is an exon?
Coding portion of a gene
What is an intron?
Non-coding portion of a gene
What is the high level architecture of a gene?
Promoter
Exons & Introns
Stop Codon
What are the processes requires to create a protein from DNA?
Transcription
Splicing
resulting in mRNA
Translation
How is the amount of protein produced determined?
Rate of transcription to pre-mRNA
Rate of splicing to mRNA
Half-life of mRNA
Rate of processing of polypeptide
How many bases encode an amino acid?
3
How are polymorphisms in the human genome defined?
A variation that has a population frequency of greater than 1%
of
A variation that does not cause a disease in its own right (although it may predispose to a common disease)
How is a mutation defined?
A gene change causing a genetic disorder
or
Any heritable change in the genome
What is the difference between classical genetic disease and multifactorial diseases?
Classical genetic disease
one mutation is sufficient to cause disease
Multifactorial disease
multiple polymorphisms cause a risk of disease
What process is necessary to allow DNA to be transcribed?
DNA has to be unpacked
What is the normal karyotype?
46 XX
46XY
What are the parts of a chromosome?
Telomere
Short arm
Centromere
Long Arm
Telomere
How can individual chromosomes be recognized?
Banding pattern with specific stains
Length
Position of centromere
What are acrocentric chromosomes?
Ones in which the short arm only contains satelite ribosomal genes, tRNAs etc
Only the long arm is really important
What is the difference between balanced and unbalanced chromosome rearrangement?
In balanced chromosomal arrangement all chromosomal material is present
In unbalanced chromosomal rearrangement there is either extra or missing chromosomal material, mostly commonly 1 or 3 copies of part of the genome
What is aneuploidy?
A whole extra or missing chromosome
What is translocation?
Rearrangement of chromosomes
What is the karotype of trisomy 21 (Down Syndrome)?
47 XY +21
47 XX +21
What is a Robertsonian Translocation?
When two acrocentric chromosomes are stuck end to end
What are the possible genotypes of the offspring of a normal father and a mother with a Robertsonian translocation?
Normal
Balanced translocation
Trisomy 14 - miscarriage
Trisomy 21 - Down Syndrome
What are the probabilites of having a second child with Down Syndrome?
Primary trisomy 21 - 1%
Robertson translocation - higher
What condition is caused by Trisomy 18
Edward Syndrome
What condition is caused by 45X karotype?
Turner syndrome
Why is X chromosome aneuploidy better tolerated?
Because of X inactivation
Which condition results from the karotype 47 XXY?
Klinefelter syndrom
What are the reproductive risks of reciprocal translocations?
50% normal chromosome or balanced translocation
large unbalanced segments - miscarriage
small unbalanced segments - dysmorphic delayed child
What is FISH used for?
Detect certain segments of DNA on chromosomes
What type of mutation leads to DiGeorge syndrome?
Deletion
(22q11)
What role does the HER2 gene play in breast cancer?
It is an oncogene.
HER2 amplification can lead to an aggressive form of breast cancer.
What molecular technique can be used to look a specific loci or chromosomes?
Quantitative PCR
How do you investigate whether a genetic variation is a polymorphism or a mutation?
Is it de-novo?
Has it been reported before?
What genes does it delete?
What is the first line chromosome test?
Array CGH
What is somatic mosaicism?
When different populations of cells (in different tissue or organs) are genetically distinct.
This occurs if recombination occurs during mitosis.
Give two examples of conditions where gonadal mosaicism is involved.
Duchenne muscular dystrophy
Osteogenesis imperfecta
What type of genes are involved in cancer?
Tumour supressor genes
(stop cells dividing)
Oncogenes
(start cells dividing)
What treatment would be used for HER2 amplification?
Trastuzamab
What treatment would be given for Philadelphia Chromosome (chronic myelogenous leukemia)?
Imatinib
What is penetrance?
The likelihood of having a disease if you have a gene mutation
What are Mendelian Disorders?
Diseases predominantly caused by a change in a single gene
What gene changes can lead to disease?
Chromosome aneuploidies
Chromosomal insertions/deletions
Subtle chromosome abnormalities
Changes in gene sequence
Insertion or deletion of a few bases
Change of a single base
What is the effect of a mutation on the promoter sequence
No transcription or reduced transcription
resulting in
no or reduced protein
What is the effect of a mutation that alters the splice consensus?
Absent or abnormal protein
What is the result of a base change introducing a new stop codon?
Absent or short protein
What is the result of a base change altering the amino acid sequence?
Different or non-functional protein
What are the types of mutation in DNA sequences?
Wild type
Stop
Missense
Insertion
Deletion - out of frame
Deletion - in frame
Triplet expansion
Is a genetic disease always caused by the same mutation?
No.
Mutations in several genes may cause the same disease.
What are the features of autosomal dominant inheritance?
Disease is seen in all generations
50% risk of affected child
Males and females equally likely to be affected
Variable disease severity
How do mutations cause disease?
Haploinsufficiency
having one working copy of the gene is not enough
Dominant negative
Abnormal protein interferes with normal protein
Gain of function
Mutation activates genes
Loss of heterozygosity
What are the features of autosomal recessive inheritance?
Two faulty copies of the gene required to cause disease
Often only one generation affected
1 in 4 risk of affected child if parents are carriers
Increased likelihood in consanguinous families
Usually cause loss of function
What is the inheritance of phenylketonuria?
Autosomal recessive
What are the features of X-linked rescessive inheritance?
If the mother is the carrier:
Female progeny will be normal or carrier
Male progeny will be normal or affected
If the father is the carrier:
All of male children will be normal (no male to male transmission)
All female children will be carriers
Why might a female carrier of an X-linked recessive disease show mild symptoms of the disease?
Skewed X Inactivation
In female cells, only one X chromosome is active
On average, half the cells have the working gene, and half have the affected gene, but this may beome skewed
How do twin studies inform genetics?
For a disease with a genetic contribution you would expect a monozygotic twin to be affected more frequently than a dizygotic twin
Give examples of 3 non-Mendelian inheritance patterns
Epigenetic modification of DNA
Mitochondrial inheritance
Somatic mosaicism
What is the clinical importance of methylation?
DNA methylation usually occurs on C bases, just before G bases and represses transcription
Methylation causes gene silencing in cancer
It is a mechanism by which the environment affects gene expression
(e.g. starvation during pregnancy)
What is imprinting?
Differences in gene expression depending on whether a gene is maternally or paternally inherited
What is Angelman’s syndrome?
Disorder of the UBE3A gene on chromosome 15
UBE3A only works in maternal copy (paternal copy is methylated)
It can occur if both copies of chromosome 15 are inherited from the father, or if there’s a new mutation in the maternal copy.
What are the features of mitochondrial inheritance?
Rare
Maternal transmission only
Male and female children equally affected
