genetics

Question 1

how do we analyse DNA?

Answer 1

lots of base pairs -> aCGH - for deletions/duplications
(chromosome/karyotype analysis for balanced rearrangements)

little BP - polymerase chain reaction (PCR) + Sanger sequencing or Next generation sequencing

Question 2

focused testing - PCR

Answer 2

allows selection of one small piece of humans genome + amplify it

-> make lots of copies of one short stretch of genome

Question 3

promotor + splice site sequence changes effect

Answer 3

stop transcription or cause abormal splicing

Question 4

effect of base change causing an amino acid change

Answer 4

change in protein sequence
- not every base change causes disease

may or may not reduce protein function
some missense mutations make protein work faster

Question 5

penetrance

Answer 5

the likelihood of having a disease if you have a gene mutation

100% penetrance = you will always get the disease if you have the mutation

Question 6

mendelian disorders

Answer 6

segregates in families
- a disease that is predominantly caused by a change in a single gene (high penetrance)

autosomal dominant, recessive, X-linked

high penetrance, small environmental contribution

Question 7

risk of female carrier’s kids being affected in Xlinked recessive inheritance

Answer 7

half her male children will be affected

half of female children will be carriers

Question 8

risk of affected male’s kids being affected in xlinked recessive inheritance?

Answer 8

all of male kids will be normal -> NO MALE TO MALE TRANSMISSION

all female kid will be carriers

Question 9

mendelian vs multifactorial

Answer 9

mendelian = high penetrance, small environmental contribution

multifactorial - genetic change is just another risk factor, penetrance for ant one mutation is low

Question 10

shared genes in mono- v dizygotic twins

Answer 10

mono - share all their genes

di - share 50% of their genes

Question 11

DNA replication happens during what phase of the cell cycle

Answer 11

S phase

DNA can be damage during replication
repair mechanisms exist - defect in these can cause disease

Question 12

mitosis

Answer 12

one diploid parent
2 identical diploid daughter cells

Question 13

meiosis

Answer 13

One diploid parent cell becomes 4 haploid daughter cells
o One of each chromosome to each cell

• Crossing over occurs – genes segregate independently, even if on the same chromosome
• Occurs in gamete formation

Question 14

Ribonucleic acid (RNA)

Answer 14

• Single stranded
• Ribose in backbone not deoxyribose
• Uracil instead of thymine

Question 15

amount of protein produced is determined by..

Answer 15

• Rate of transcription – manufacture of pre-mRNA
• Rate of splicing to mRNA
• Half life of mRNA
• Rate of processing of polypeptide

Question 16

polymorphisms

Answer 16

• any variation in the human genome that has a population frequency of more than 1%
• OR
• Variation in human genome that does not cause disease in its own right
  o May however predispose a common disease

Question 17

mutation

Answer 17

• A gene change that causes genetic disorder
  OR
• Any heritable change in human genome

Question 18

chromosome changes that cause disease - balanced vs unbalanced chromosome rearrangement

Answer 18

Balanced chromosome rearrangement
o All the chromosomal material is present

Unbalance chromosome rearrangement
o Extra or missing chromosomal material
o Usually 1 or 3 copies of some of the genome
–>(developmentally bad news)

Unbalanced rearrangements = multiple malformations or miscarriage

Question 19

aneuploidy

Answer 19

whole extra or missing chromosome

Question 20

robertsonian translocation

Answer 20

2 acrocentric chromosomes stuck end to end

increased risk of trisomy in pregnancy

Question 21

edwards syndrome, turners, klinefelter

Answer 21

47XY + 18 = Edward syndrome (trisomy 18)

45 X = Turner syndrome

47 XXY = Klinefelter

Question 22

is x chromosome aneuploidy better or worse tolerated? why?

Answer 22

X chromosome aneuploidy is better tolerated because of X inactivation

Question 23

reproductive risks of reciprocal translocations

Answer 23

50% of conceptions will have either normal chromosomes or the balanced translocation

• Unbalanced products result in –
  o Miscarriage – large segments
  o Dysmorphic delayed child – small segments

Question 24

molecular technique for genome wide testing

Answer 24

array comparative genomic hybridisation (aCGH)

Question 25

molecular testing for specific chromosome

Answer 25

quantitive PCR

Question 26

microoarray CGH

Answer 26

• Detects any missing or duplicated piece of chromosome
• Causative deletions possibly in up to 7% of children with learning disability
• Many deletions seen are neutral polymorphisms
• 1st line chromosome test!

Question 27

how do deletions appear on aCGH?

Answer 27

half as much as DNA indicates a deletion