MTM WK6 - MUTATIONS & GENETIC DISEASES

Question 1

GENOME VARIATION

Answer 1

changes in number or structure of chromosomes e.g. DNA substitution or deletion

Question 2

PATHOGENIC GENE VARIATION

Answer 2

variation that disrupts gene function

Question 3

CAUSES OF MUTATIONS (4)

Answer 3

• errors in DNA rep.
• UV - covalently binds 2 adjacent thymines (BAD)
• ionising radiation - breaks in DNA
• chemicals - breaks in DNA

Question 4

POLYMORPHISMS

Answer 4

non-harmful mutations e.g. silent or substitution

Question 5

SINGLE NUCLEOTIDE POLYMORPHISM (SNP)

Answer 5

change in single base at particular position e.g. most ppl have C at one place but some have T (>1%)

Question 6

DNA SEQUENCING (used to look for bases)

Answer 6

• amplify tiny amounts of target DNA & use DNA as template to generate set of fragments that differ in length from each other then sequence fragments by size, identify bases at end & recreate original DNA sequence
• determine exact location & type of mutation

Question 7

ENDOGENOUS (inside) MECHANISMS CAUSING DNA DAMAGE (3)

Answer 7

• DEPURINATION (deletion mutation of A or G due to splitting of purine-sugar bond)
• DEAMINATION (cytosine randomly deaminated to uracil)
• CYTOSINE METHYLATION (cytosine deaminate to form thymine)

Question 8

GERMLINE MUTATION

Answer 8

mutations in egg/sperm which are heritable

Question 9

SOMATIC MUTATIONS

Answer 9

non-heritable mutations in non-germline tissues

Question 10

CHECKS FOR DNA REPLICATION SUCCESS (3)

Answer 10

• G2 checkpoint checks DNA
• DNA polymerase checks for issues as it adds bases
• mismatch proteins (excise newly synthesised mismatch & use template strand to re-synthesise new one)

Question 11

REPAIRING OF DOUBLE-STRANDED DNA BREAK

Answer 11

use ligands to pair ends of broken strands (leads to deletion of some nucleotides)

Question 12

MISSENSE MUTATION

Answer 12

substitution where new code codes for different amino so dif. primary so dif. tertiary

Question 13

NONSENSE MUTATION

Answer 13

substitution mutation which codes for stop codon

Question 14

SPLICE-SITE MUTATION

Answer 14

occur where splicing is meant to occur (leads to altered RNA sequence)

Question 15

COPY NUMBER MUTATIONS

Answer 15

insertion/deletion caused by unequal crossing over between repeat sequences (as there are too many repeats)

Question 16

LIGHT VS DARK BANDS OF CHROMOSOME

Answer 16

light replicates earlier & has less condensed chromatin

Question 17

WAYS WE EXAMINE CHROMOSOMES (3)

Answer 17

Karyotype, FISH, array CGH

Question 18

KARYOTYPE (lowest resolution)

Answer 18

get sample of blood –> separate RBC –> add cultured medium to suspension –> incubate for 3 days at 37 –> add something that stops cell division –> fix cells –> stain cells –> photograph cells –> organise cells into karyotype –> examine chromosomes for errors

Question 19

FISH

Answer 19

create fluorescent probes to hybridise specific area of chromosome then hybridise patient DNA & look for fluorescent markers (e.g. light up if chromosome present)

Question 20

ARRAY CGH

Answer 20

• hybridise both the test genomic DNA & normal reference DNA in DNA microarray containing probes representing genomic regions of interest (DNAs compete for same probe site on microarray)
• if reference & test DNA are same then you get one middle colour but if patient doesn’t have chromosome in a part, it fluoresces

Question 21

KARYOTYPE NOMENCLATURE OF ABNORMALITIES

Answer 21

number of chromosomes —– sex chromosomes —- abnormality e.g. 47,XX,+21 (down syndrome as 1 extra chromosome & +21)

Question 22

NON DISJUNCTION

Answer 22

cell doesn’t divide properly so one daughter has 2 copies of chromosome & one daughter has 0

Question 23

ANEUPLOIDY

Answer 23

change in number of a specific chromosome (trisomy = 3 copies of chromosome) (monosomy = 1 copy (1 less than usual)

Question 24

POLYPLOIDY

Answer 24

change in overall chromosome number (triploidy = extra set of chromosomes (3 sets)) (tetraploidy = 2 extra sets of chromosomes (4sets/92 pair)

Question 25

WHY TRISOMY 21 (downs (3 copies of chromosome 21)) RISK INCREASES WITH MATERNAL AGE

Answer 25

meiosis 1 occurs at ovulation & meiosis 2 only occurs at fertilisation BUT eggs are made from puberty so wear & tear over age

Question 26

KLINEFELTER SYNDROME

Answer 26

47, XXY (male has extra X which leads to tallness, infertility, poor secondary sexual characteristic)

Question 27

ROBERTSONIAN TRANSLOCATION

Answer 27

breakage of 2 acentric chromosomes (13,14,15,21,22) at centromeres & then their long arms fuse (accrocentric chromosomes have their centromere close to one side so short arm is shorter than usual & lost at fusion) (look at image on album)

Question 28

RECIPROCAL TRANSLOCATION

Answer 28

breakage of 2 homologous chromosomes (not just acentric ones) with exchange of their functions