Genetic Flashcards
What are telomers
Region of repetitive nucleotide sequence at the end of each chromosome which protects the chromosome from deterioration and fusion
Which are purines and which are pyrimidines
-Adenine
-Thymine
-Cytosine
-Guanine
-Purine: Adenine, Guanine
-Pyrimidine: Thymine, Cytosine
What are the purpose of these enzymes
-DNA polymerase
-Helices
-Ligase
-DNA polymerase: creases DNA molecules by assembling nucleotides
-Helicase: disrupts the DNA double bond to allow replication
-Ligase: DNA repair enzyme
How do you calculate carrier incidence and carrier frequency
Carrier Incidence: carrier frequency x carrier frequency x4
Carrier frequency: square root (carrier incidence/4)
“Incidence = frequency squared x 4
What is the difference between allelic and locus heterogeneity
-Allelic: more than one mutation in a gene (e.g. CF)
-Locus: mutations of more than one gene (e.g. TS)
What is the difference in these mutations
-missense
-silent point mutation
-nonsense mutation
-splicing mutation
-missense: point mutation results in codon change that causes a amino acid change e.g. sickle cell disease (A instead of T)
-Nonsense mutation: point mutation that results in a stop codon
-Silent mutation: codon change but same amino acid is still encoded for. Natural genetic variability
-Splicing mutation: failure to remove introns from transcripts DNA so intron DNA is left in the RNA molecule causing abnormal protein
Describe the concept of Anticipation
More triplet repeats occur in successive generations = increased severity of disease
What is penetrance
The presence/absence of a disease or trait. Must have both the phenotype and genotype
What is the difference between expressivity and penetrance
Penetrance= genotype + phenotype. Presence of disease both on person and in genome
Expressivity= variation in the clinical features of a mutation e.g. NF1
In consanguinity what is the risk of having a major problem
-Background risk
-Incest
-1st degree cousins
-2nd degree cousins
-3%
-50%
-6% (double)
-4%
Describe splice site mutation
Splicing- removal of non-coding introns
Mutation is splicing allows this non-coding material to be translated into the RNA. Results in mutation in end protein
Describe anticipation
Seen in triple repeat disorders. More aggressive and earlier disease in subsequent generations
What type of disorder is Myotonic muscular dystrophy
What is the genetic defect
What are the symptoms
Triplet repeat disorder
-CTG expansion mutation
-SX: facial hypotonia with V shaped lip, muscle weakness, heart condition issues, IQ/Behavioural issues
What type of mutation causes Fredrick ataxia
What is the gene
What age of onset
What are the symptoms
Triplet repeat mutation
FXN gene- GAA triplet repeat mutation = results in loss of function mutation
FXN gene encodes a mitochondrial protein that is used to chaperone iron. Mutation - iron accumulation and oxidative damage
Age onset: teenage years
Sx
-Brain: ataxia, peripheral neuropathy, loss of proprioception and vibration, loss deep tendon reflexs
-Muscle: weakness, kyphosis, foot deformity
-Heart: HOCM
-Endo: diabetes mellitus
What condition does a mutation in FMR1 gene cause
Fragile X
“Fragile Mother Related 1”
What does a mutation in FXN cause
Fredrick Ataxia
“Fredirick ataXiaN gene”
What study to do you use to check for Beckwith-Weidmann
Methylation specific multiple ligand probe analysis
What conditions will a microarray detect vs not
Detect: micro deletion, micro duplication, aneuploidy, unbalanced translocation, uniparental disomy if SNP analysis used, long stretches of homogeneity (SNP)
Won’t detect: balanced translocation, methylation abnormalities, triple repeat, single nucleotide
What test would be used for NF1 or Marfans
Sanger sequencing- will detect a mutation on a nucleotide level
What test is used for analysis of myotonic muscular dystrophy
triple repeat analysis - PCR reaction that is then analysed with southern blot to see the length of triplet repeats
What is the difference between western and southern blot
Western blot- protein analysis
Southern blot- DNA analysis
Describe the phases of mitosis
-interphase: DNA replicates. Go from 46 –> 92 chromatids
-prophase: formation of microtubules. nuclear envelop dissolves. Microspindles attache to each chromosome
-metaphase: chromosomes lined up along the equator (metaphase plate)
-anaphase: chromosomes pulled to separate ends of the cell by the microtubles
-Telophase: nuclear envelope reforms around opposite cluster of DNA
-Cytokinesis: remained of cell and cytoplasm divides to make 2 daughter cells
What is the gamete result if you have non-dysjunction in meiosis I vs meiosis II
Meiosis I: all the cell lines affected. 2 cells have N+1, 2 cells have N-1
Meiosis II: happens after the first division, so of the 4 cells produced, 2 won’t be affected. Of the remaining 2, 1 will gain (N+1) and one will loose (N-1)- therefore 4 gametes: 2 normal, 1 N+1, 1N-1
What is a Robertsonian chromosome and which are they
Contain an non central centromere. The DNA in the short arm (p arm) is redundant
Chromsomes 13, 14, 15, 21 and 22
In a maternal carrier of a translocation between T14 and T21, what is the hypothetical risk of having an abnormal gamete vs the actual risk
In theory, you only have a 1/6 chance of normal, 1/6 chance balance translocation, 1/6 chance T21 and then a 1/6 chance of T14, 1/6 chance of -21, 1/6 chance of -14
In reality, zygotes except normal, balance and T21 are non-viable so you risk of recurrence is 1%
What abnormal results on Quad screening would you expect for the 3 trisomies (21, 18, 13) and Turners Syndrome
T21: “HIgh” High hCG and Inhibin A
T18 “HE is low”- hCG and estriol
T13: “AFPateau is low” - low AFP
Turner: HIgh- high hCG and Inhibin A
What is the most consistent features of Turners syndrome and what is it due to
Short stature
Loss of the SHOX gene on the short arm of the X chromosome
You see a baby with puffy hands and feet and consider the diagnosis of congenital lymphoedema.
What condition should you screen for
Turners syndrome
