genetics Flashcards
What are the 2 contributing factors to acquiring a disease?
genetics and environment
Detail the structure of DNA
strands of DNA pair up in an antiparallel fashion
replicated and read in 5’ to 3’ direction
information held in base sequence in sugar phosphate backbone
What are chromosomes?
DNA strand associated with protoeins (histones) and is wound into a chromsome
What is the cell cycle?
When does DNA synthesis occur?
G1 - S - G2 - M - G1
DNA synthesis occurs in the s phase
Detail the roles of DNA helicase, DNA polymerase, DNA ligase
DNA H - unwinds DNA
DNA polymerase - copies 5-3 strand and copies 3-5 strand in okazaki fragments
DNA ligase - joins the fragments together
What is mitosis?
One diploid parent becomes 2 identical diploid daughter cells
Meiosis
One diploid parent cell becomes 4 haploid daughter cells
crossing over occurs
gametes and formed
What are the sequence variations within a gene?
changes in promoter sequence and exon sequence
What are some sequence changes in DNA between genes?
D+D?
single nucleotide polymorphisms - larger deletions or duplications
What is a polymorphism?
any variation in the human genome which has a population frequency of greater then 1%
does not cause disease in its own right but may predispose someone to acquiring a disease
What is a mutation?
gene change that causes genetic disorder
any heritable change in the human genome
multifactorial disease =
multiple polymorphisms cause risk of disease
What is a normal female chromosome?
46 XX
What is an unbalanced chromosome rearrangement?
Extra or missing chromosomal material
usually 1 or 3 copies of the genome
Aneuploidy?
whole or extra missing chromosome
translocation
Rearrangement of chromosomes
What does 47 XY + 21 create?
down syndrome, trisomy 21
47XY + 14?
miscarriage, trisomy 14
47 XY + 18
Edward syndrome - trisomy 18
45 X
turner syndrome
47 XXY
klinefelter syndrome
What is robertson translocation?
two acrocentric chromosomes stuck end to end, increased risk of trisomy in pregnancy
When is microarray CGH used?
1st line chromosome test, detects any missing or duplicated piece of chromosome - finds polymorphisms
What is mosaicism?
Gonadal and somatic?
Mosaicism occurs when a person has two or more genetically different sets of cells in his or her body. If those abnormal cells begin to outnumber the normal cells, it can lead to disease that can be traced from the cellular level to affected tissue, like skin, the brain, or other organs.
different cells have a different genetic constitution -
Gonadal:
causes recurrence risk for autosomal dominant conditions even if parent is unaffected
somatic - all cells suffer as they divide, but repair mechanisms exist
What are tumour suppressors?
genes stop cells dividing if switched on
What are oncogenes?
some genes start cells dividing when switched on
What is pentrance?
the likelihood of having a disease ( if you have a mutation)
What is the definition of gene expression?
variation in disease severity if you have the mutation
When is aCGH used? - what does it check for?
1st line for paediatric referrals, checks for deletions or duplications
How does PCR work?
one small piece of human DNA and amplify it
What are the different types of mutations?
Stop transcription and abnormal splicing
missense?
nonsense?
another one that involves the bases
promotor and splice site sequence changes - stop transcription and cause abnormal splicing
base changing causing amino acid change (missense)- change in protein sequence, may or may not reduce protein function
base changing causing premature stop codon ( nonsense)
insertion or deletion of bases
What is a mendelian disorder?
a disease that is caused by a change in a single gene
Describe some factors of autosomal dominant genes
disease seen in all generations, 50% risk of child being affected, same risk for males and females
Autosomal recessive?
how many generations are usually affected?
what is the penetrance risk?
What increases the likelihood of recessive conditions in families?
2 faulty copies of the gene needed to cause disease
only 1 generation usually affected
1 in 4 risk of an affected child if parents are carriers
increased likelihood of autosomal recessive conditions being apparent in consanguineous families
Describe an X- linked condition
recessive, y chromosome irrelevant, mother carrier then 50% of daughter carrier and male affected
NO MALE TO MALE TRANSITION
X- inactivation -
What happens in females?
cell only requires 1 working copy of X chromosome
females - each cell has a random X chromosome inactivated
What is mitochondrial DNA important for and how is it inherited?
mitochondrial metabolic pathways and ribosomal RNA
inherited almost exclusively maternally
What is haploinsufficiency?
How do mutations affect proteins?
only have 1 working copy is not enough - haploinsufficiency
abnormal protein interferes with normal protein
mutation activates gene - gain of function mutation loss of heterozygosity
What does DNA methylation lead to?
modifications of histones which repress transcription
What is imprinting?
where is it found? - what is contained in these regions?
differences in gene expression depending paternal or maternal inheritance
specific chromosomal regions contain imprinted genes
Such regions usually contain both maternally and paternally imprinted genes
What are some symptoms of angelmann-syndrome?
What chromosome is it found on?
neuro genetic disorder - developmental delay, intellectual disability, happy demeanour
chromosome 15
What is heteroplasmy?
different daughter cells contain different proportions of mutant mitochondria
What are the characteristics gained by cells on progression to cancer?
increase growth signals, remove growth suppression, avoid apoptosis, achieve immortality, become invasive, make own blood supply (angiogenesis), loss of DNA spell checks, avoid immune system
What are mechanisms of gene activation?
duplication of gene, activation of the gene promoter, change in amino acid sequence
What is FISH?
fluorescence in situ hybridisation
light up specific bit of chromosome
What gene causes breast cancer?
BRCA1 - small proportion of familial breast cancer
What is BRCA1 gene involved with?
DNA strand repair
frame-shift mutation?
nucleotide insertion mutation - altered transcription and translation of every codon found
after the mutation.
Can you be a carrier of an autosomal gene?
No such thing
Only a 50% of having a child that is affected
