Flashcards in Genetics 1, 2, 3, 4 - Human genome, chromosomes and cell division, how genetics cause disease Deck (111):
What 2 factors causes all disease?
Genetics and environment
In what direction is DNA always replicated and read?
5 to 3 direction
Bases in DNA?Bases in RNA?
DNA = ACGTRNA = ACGU
In DNA what bases pair?
Thymine and AdenineGuanine and Cytosine
In the nucleus, what is DNA wound around?
Proteins including histone proteins
What are genes?
Short sections of DNA - code for a specific protein by determining the order in which amino acids should be joined
What are chromosomes?
a thread-like structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes.
What are the 2 main phases of the ell cycle?
What happens during interphase?
The cell grows, accumulating nutrients needed for mitosis and duplicating DNA
What are the parts of interphase?
G1 - the cell makes new proteins for DNA synthesisG0 - the cell carries out its normal activitiesSynthesis - the cell replicates its DNAG2 - the cell prepares to divide
What happens during the mitotic phase?
The cell splits itself into 2 distinct cells (daughter cells)- genetically identical
What are the checkpoints in the cell cycle and what does each check?
G1 checkpoint = is the cell big enough and the environment suitable (if not, goes to G0)G2 checkpoint = has the DNA replicated, is the cell big enough, and the environment suitable?Mitosis checkpoint = are the chromosomes aligned on the spindle?
How many pairs of chromosomes does the normal human have?
What type of DNA damage can occur during replication? (3)What conditions mean that you cannot repair these damages?
DNA strand breaks (BRCA1/2)Chemical cross linking (Xeroderma pigmentosa)Mismatched base (hereditary colorectal cancer)
What happens during mitosis?
1 diploid parent cell becomes 2 identical diploid daughter cells
What happens during Meiosis?
a diploid cell, ordinarily having two complete sets of chromosomes, gives rise to 4 haploid cells (gametes) each having one set of genetically different chromosomes (germ cell forms either 4 sperm or 4 egg cells)
What are the stages in meiosis?
DNA replicates and recombines (crossing over occurs)Cell division 1Cell division 2
How are the chromosomes produced during meiosis genetically unique?
Due to crossing over
How is RNA different to DNA?
Single strandedRibose is backbone instead of deoxyriboseUracil is used instead of thymine
What parts of DNA are spliced out after transcription?
What is the amount of protein produced determined by? (4)
Rate of transcription (manufacture of pre-mRNA)Rate of splicing to mRNAHalf life of mRNARate of processing of polypeptide
What converts DNA to pre-mRNA?
What converted pre-mRNA to mRNA?
What converts mRNA to protein?
What do 3 bases encode?
1 amino acid or a stop
What is a polymorphism?
The occurrence of a chromosome or a genetic character in more than one form, resulting in existence of more than one morphological type in the same population (population frequency of greater than 1%) - variation in the human genome that does not cause a disease it its own right but may however predispose to a common disease
What is a single nucleotide polymorphism?
a DNA sequence variation occurring when a single nucleotide - A, T, C, or G - in the genome (or other shared sequence) differs between members of a species (or between paired chromosomes in an individual)
What is a mutation?
Disease causing genetic change
What does a mutation in FGFR3 cause?
What are the 4 stages of mitosis?
What is a chromatid?
One of the 2 copies of the DNA that are joined at the centromere and make up the chromosome during cell division
What happens during prophase?
The chromosomes appear condensed and the nuclear membrane disappears
What happens during metaphase?
The chromosomes line up along the metaphase plate
What happens during anaphase?
The chromatids of each chromosome are separated and pulled apart to opposite ends of the cell
What happens during telophase?
The chromosomes are at either poles of the cell and the nuclear membrane reappearsThe cytoplasm starts to divide
What is a karyotype?
The number and appearance of chromosomes in the nucleus of a eukaryote cell (picture of the chromosomes)
What are the darker areas in a karyotype?
The areas of DNA that have less genes
How many autosomes does a human have?
22 pairs = 44
Parts of a chromosome?
TelomereShort arm (p)CentromereLong arm (q)Telomere
How many divisions can the average cell make?
60 - 100
What is phenotype?
the observable characteristics of a person which result from his genotype and the environement
What is an acrocentric chromosome?
A chromosome in which the centromere is located quite near one end of the chromosome. Humans normally have five pairs of acrocentric chromosomes
Parts of an acrocentric chromosome?
Satellite ribosomal genes, tRNAs, etc.CentromereLong arm
What is satellite DNA?
very large arrays of tandemly repeating, non-coding DNA
Are polymorphisms usually inherited?
Effect of balanced chromosome rearrangement on overall chromosomal material?
All the chromosomal material is present
Effect of unbalanced chromosome rearrangement on overall chromosomal arrangement?
Extra or missing DNA material (usually 1 or 3 copies of some of the gene)
Whole extra or missing chromosome
Rearrangement of chromosomes
What are microdeletions?
Deleted parts of DNA that cannot be seen down a microscope due to their size
What 3 types of genetic variations can be seen down a microscope?
AneuploidyTranslocationInsertions and deletions
What type of karyotype difference will a patient with downs syndrome have?
3 copies of chromosome 21 (doest matter where the extra copy is e.g. can be separate or translocated - attached to another chromosome)
What is nondisjunction?
When a pair of chromosomes fails to separate during egg (or sperm) formation = extra copy of a chromosome e.g. downs syndrome
Is downs syndrome inherited?
No - it is usually caused by dysjunction (unless caused by a Robbertsonian translocation)
What is a Robertsonian translocation?
2 acrocentric chromosomes stuck end to end
What is trisomy?
One extra chromosome present in each cell
What is the condition caused by trisomy 21?
What does a robertsonian translocation cause an increased risk of in a pregnancy?
What will trisomy 14 cause?
What will trisomy 18 cause?
Edward syndrome - either miscarriage or baby will die within the first few days of life)
What does 45 X cause?
Turner syndrome - female of normal intelligence (Infertile - problem with ovary development)
What does 47 XXX cause?
Triple X syndrome
What does 47 XXY cause?
Klinefelter syndrome - presence of Y chromosome = male
What is a reciprocal translocation?
When 2 fragments break off from 2 different chromosomes and swap places
What is monosomy?
Absence of one chromosome of a pair of homologous chromosomes e.g. turners
What do reciprocal translocations result in in terms of reproduction?
50% = normal or balanced translocation Unbalanced products = miscarriage if large segments or dysmorphic delayed child if small segments
What is FISH?
Fluorescence in situ hybridisationTechnique used to rapidly look for specific micro deletions and also for gross alterations in chromosomal numberFluorescent dye is attached to probe DNA that attaches to the chromosomal region of interest - if region present, the dye fluoresces
What is HER2?
Human epidermal growth factor - protein that can affect the growth of some cancer cellsIt is found on the surface of normal breast cells - some breast cancer cells have a very high number of HER2 - extra HER2 receptors stimulate the cancer cells to divide and grow
What is array comparative genomic hybridisation (aCGH) used for?
To detect any missing or duplicated pieces of chromosome in a patient sample by comparing it to a control sample
What is a locus?
The specific location of a gene on a chromosome
What is used to analyse one single piece of a human genome?
Quantitive PCR (specific loci/ chromosomes) - make lots of copies of part of the genome
If aCGH does show a missing piece of chromosome, what must you decide?
Is it disease causing or a polymorph (could test parents)
What is the first line chromosome test?
What is mosaicism?
different cells in the same individual have different numbers or arrangements of chromosomes (caused by a mutation during development)
What is somatic mosaicism?
Affecting cells other than egg or sperm cells
What is gonadal mosaicism?
Affecting only egg or sperm cells
What 2 diseases are gonadal mosaicism commoner in?
Duchene muscular dystrophyBrittle bone disease(causes recurrence risk for autosomal dominant conditions even if parent is unaffected)
What cancer is the Philadelphia chromosome associated with?
Leukaemia (imitanib used to target this)
What monoclonal antibody is used to target HER2?
What are the 4 ways in which we can analyse DNA?
Chromosome analysis (karyotyping)aCGH (for deletions/ duplicaitons)PCR and Sänger sequencingNext generation sequencing
What is an example of genome wide testing?
What is an example of focused genome testing?
What are the 3 stages of PCR?
-Denaturation (DNA is heated to 100 degrees causing the 2 DNA strands to separate)-Primer annealing (DNA is cooled to 50 degrees to allow the primers to anneal)-Extension (the DNA is heated to approx. 72 degrees to allow tax polymerase to extend the DNA molecule)
What are alleles?
Different versions of the same gene
What is performed after PCR in order that the sequence of bases in a gene can be read?
Sequencing (2 genes are sequenced over each other meaning when being read on a machine, if there is a mutation there will be an overlap where there are 2 different bases)
What will the effect of a promotor mutation be?
No, or reduced transcription = no or reduced protein
What will the effect of a mutation in a splice consensus be?
Abnormal or absent protein
What will the effect of a mutation causing a base change making a new stop be?
short or absent protein
What is the consequence of a mutation causing an alteration in the amino acid sequence?
Different or non-functioning protein
What is a point mutation?
A mutation affecting only one nucleotide - can be a polymorphism or can cause a serious disease
What are the 3 possible results of a point mutation?
What is a missence mutation?
A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid
What is a nonsense mutation?
a point mutation in a sequence of DNA that results in a premature stop codon
What is an in frame deletion?
An in-frame deletion must involve at least 3 DNA bases (it may be more and is usually multiple of 3) removes an entire codon and so may lead to the deletion of an amino acid from a protein
What is an out of frame deletion?
an out-of-frame deletion changes the reading frame and gives rise to an amino acid sequence which following the deletion is completely different from the native sequence
What is an NGS machine?
A DNA sequencer
What are the possible types of genetic changes?
A disease causing mutationA polymorphismA variant of unknown significance
What is a de-novo mutation?
A new mutation
What is used to find the mutation that matters among millions of polymorphisms in gene sequencing?
What is penetrance?
Likelihood of getting the disease if you have the mutation (100% penetrance means you will always get the disease)
Penetrance of BRCA1 gene?
What is a mendelian disorder?
A disease that segregates in families in the manner predicted by Mendel's law (essentially a disease that is predominantly caused by a change in a single gene) e.g. autosomal dominant, recessive X-linked
On a family tree, what is the symbol for men and women?
Men = squareWomen = roundLine through symbol = died
On a family tree, what is the symbol for miscarriage?
What is the chance of a child being affected by an autosomal dominant condition if a parent is affected?
Why may a female carrier of a X-linked disease show mild features of it?
Due to X inactivation
What is X inactivation?
In order to provide gene-dosage compensation in females, 1 of the 2 X chromosomes in each cell are inactivated - the process for choosing which is turned off is randomThis means if she is a carrier of an x-linked condition then there may be some mutated genes activated
What gene is essential for X inactivation?
XIST gene (methylation is one mechanism for X inactivation)
When dose skewing of X inactivation occur? (4)
When one X chromosome carries a cell-lethal mutationMutation in one XIST geneWith balanced X; autosome translocationBy chance
In terms of gene/ environment causation of phenotype, what has the largest impact in a rare genetic disease?