Genetics

Question 1

what is the Difference between constitutive and regulated gene expression?

Answer 1

Constitutive :Products made by all cells all the time - often called ‘housekeeping’ genes. Expression is constant.
Regulated: Time (developmental), place (cell type), amount, in response to signals. Can be under very tight control


Question 2

~20,000 genes but many more (millions??) proteins. Protein diversity is increased and can occur because?

Answer 2

Many genes have more than one promoter.

Alternative splicing

Question 3

mechanisms for chromatin remodelling using epigenetic marks (5)?

Answer 3

o histone modifications (acetylated in euchromatin; methylated or hypo-methylated depending on histone variant).
o DNA methylation (NB methylation of CpGs (often around promoters)lead to silencing of genes).
o nucleosome positioning.
o non-coding RNAs.
o nuclear location of chromatin.

Question 4

Differences between euchromatin and heterochromatin?

Answer 4

eu = open, relaxed. Hetero = closed, condesned

Question 5

what percentage of the human genome is responsible for protein coding seqeunces

Answer 5

1-2%

Question 6

Factors involved in basal gene expression (3)?

Answer 6

open chromatin, RNA polymerase, basal transcription

factors that interact with promoters (DNA) and various proteins.

Question 7

Factors involved in regulated gene expression (6)?

Answer 7

same as above (open chromatin, RNA polymerase, basal transcription factors that interact with promoters (DNA) and various proteins.) + enhancers/silencers (DNA), more
transcription factors, long non-coding RNAs

Question 8

• Basic steps in gene expression

Answer 8

open conformation of chromatin.
Transcription.
Post-transcription processing.
Translation.
Post Translation processing.
Protein targeting and transport.

Question 9

what does biallelic mean?

Answer 9

gene is expressed from both maternal and paternal copy

Question 10

consequenes of monoallelic expression?

Answer 10

for some genes its sufficient. Others its not. Some it IS ESSENTIAL (X inactivation)

Question 11

Inactivation of genes on the X chromosome and genomic imprinting is mostly determined by epigenetic mechanisms. name them (3)

Answer 11

Histone modifications, DNA methylation and Non-codingRNAs

Question 12

what is the inactived X chromosome called

Answer 12

Barr Body

Question 13

describe X chromosome inactivation

Answer 13

occurs in early embryogenesis and starts with expression of Xist – a long non-coding RNA, leading to heterochromatin formation spreading along the chromosome; DNA methylation also plays a role.

Question 14

is the whole chromosome switched off in x inactivation

Answer 14

no, Some genes on the X chromosome escape X inactivation because they need to be expressed biallelically

Question 15

definition of genomic imprinting

Answer 15

a phenomenon by which certain genes can be expressed in a parent-of-origin-specific manner

Question 16

Genomic imprinting involves which epigenetic mechanisms (3)?

Answer 16

DNA methylation, Chromatin condensation (including histone modifications), Non-Coding RNAs

Question 17

• Mechanisms that can give rise to disorders of imprinting (4)

Answer 17

Deletion or duplications of regions of imprinted genes (Loss of Heterozygocity).
Uniparental Disomy (UPD) - both chromosomes from mother or father.
Epimutations - loss of imprinting
DNA mutations in imprinted genes

Question 18

how does UPD occur (4)?

Answer 18

1: Meiotic non- disjunction in both gametes (egg has 2 chromosome and sperm has none. or vice versa).
2: Meiotic non- disjunction in one gamete followed by duplication in zygote (egg has 1 chromosome, sperm has none and egg is duplicated. or vice versa).
3: Loss of one chromosome in zygote and duplication of other chromosome.
4: Meiotic non-disjunction in one gamete followed by loss of chromosome in zygote (egg has 2 chromosome, sperm has one, sperm is lost in zygote. or vice versa).

Question 19

what is BW syndrome? what is the majority of causes?

Answer 19

Beckwith-Weidemann syndrome is an imprinting disorder linked to imprinted genes on chr 11p15.5.
Majority caused by epimutations on maternal allele.

Question 20

what are PW syndrom and Angelmann syndrome? what are their causes.

Answer 20

are imprinting disorders linked to imprinted genes on chr 15q. PWS due to deficiency of paternally expressed genes (P or paternal). AS essentially due to a deficiency of maternally expressed genes

Question 21

pattern of inheritance for Mutations in an active paternal/inactive maternal?

Answer 21

male carriers and affected males can have affected children but not carrier children.
Female carriers and affected females can have carrier children but not affected children

Question 22

Pattern of inheritance for Mutations in an active maternal/inactive paternal?

Answer 22

female carriers and affected females can have affected children but not carrier children.
Male carriers and affected females can have carrier children but not affected children.

Question 23

what percentage of babies have a birth defect?

Answer 23

4%

Question 24

what are the most common autosomal and sex chromosomal defects respectively?

Answer 24

Trisomy 21 and Klinefelter Syndrome (XXY).

Question 25

describe the relationship b/w age of a woman and risk of child having T21.

Answer 25

increases with age, especially in late 30s and 40s

Question 26

questions in an ideal family history?

Answer 26

get up to 2nd degree history, inherited family condition, recurrent miscarriages, unexplained perinatal deaths, consanguinity, ethnic background

Question 27

• Reasons why a woman/couple choose to have prenatal testing? (4)

Answer 27

provides risk information.
Termination option.
Allows couple to psychologically prepare.
Allow medical and allied health staff plan management and care of baby

Question 28

dif b/w prenatal screening and diagnostic testing.

Answer 28

Prenatal screening tests give a risk figure and are non-invasive (to the pregnancy), diagnostic
tests give a more definitive result and are (currently) invasive. NB BUT non-invasive prenatal testing can give a definitive result, and chromosomal microarrays can give results of uncertain clinical significance.

Question 29

• Currently 2 prenatal screening tests in major use are?
what conditions these tests give a risk for? what is measured? when tests are carried out? what other factors are used in providing the risk figure? the cut-off for T21?

Answer 29

First trimester combined screening. Tests for T21 and T18 defect. Blood taken at 10 weeks (measure analytes), ultrasound at 13 weeks. In ultrasound measure neuchal translucency (oedema behind head) and crown rump. other factors are maternal age, weight. Cut off for T21 is 1/300.

Second trimester maternal serum screening. Test for T21, 18 and neural tube defect. Blood taken at 16 week (measure analytes). also use maternal age, weight. Cut of for T21 is 1/250.

Question 30

NIPT – what is analysed? What technology is used? What can be detected?

Answer 30

Non-Invasive Prenatal Test. Cell free fetal DNA/RNA in maternal blood

Question 31

• Fetal sampling procedures: CVS vs amniocentesis – how they differ?

Answer 31

CVS (Chorionic villus sampling) - 11 weeks, placental tissue, ultrasound, invasive - risk of miscarriage 1%.

Amnio - 15 weeks, amniotic fluid, ultrasound, invasive - risk of miscarriage half of above (.5%). if TOP requested - labour induced.

Question 32

Types testing for chromosomes (3)?

Answer 32

o FISH – fluorescent tags for specific chromosomes, interphase, fast result, looks for aneuploides.
o Karyotype – requires dividing (metaphase) cells, chromosomes stained, aligned and counted, result takes 2 weeks, looks for aneuploides and chromosomal rearrangements (but can’t see microdeletions/microduplications – resolution too low).
o Chromosomal microarray –a molecular test – looks for copy number variation (some also include SNPs) – can detect microdeletions/microduplications because resolution is higher – BUT can also get results of uncertain clinical significance.

Question 33

causes of Down Syndrome?

Answer 33

95% cases due to standard trisomy 21 caused by non-disjunction. 5% due to unbalanced translocations. 1-2% inherited.

Question 34

Differences between balanced and unbalanced translocations?

Answer 34

Translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of chromosome material is unequal resulting in extra or missing genes).

Question 35

how is termination of pregnancy performed if requested in a CVS

Answer 35

dilatation & curettage (D&C) under general anaesthetic.

Question 36

what 4 analytes are measured in 2nd trimester screening?

Answer 36

10 AFP.
Oestriol.
HcG.
Inhibin A.

Question 37

in 2nd trimester screening what are the analyte results that give an increased risk of T21?

Answer 37

↓ AFP, Oestriol ↓, Hcg↑, Inhibin A↑

Question 38

Robertsonian translocation?

Answer 38

translocation between two ACROCENTRIC (only) chromosomes (13, 14, 15, 21, 22)