MRCOG Part 1

Question 1

What components make up a nucleotide? And what bond joins each nucleotide to the next?

Answer 1

Pentose sugar, phosphate group and nitrogenous base

Phosphodiesterase bond

Question 2

Types of blotting and what they look for

Answer 2

South D(own)NA
North RNA
West Protein

Question 3

Types of nitrogenous bases and examples

Answer 3

Purine - Guanine and Adenine

Pyrimidine - Cytosine and Thymine (DNA)/Uracil (RNA)

Question 4

Structure of DNA and general replication steps

Answer 4

Double stranded helix with hydrogen bonds, anti parallel pairs.

Replication involves unwinding of DNA by helicase to separate strands of DNA

DNA is copied by DNA polymerase using one strand as template

Ligase winds DNA back together when temperature drops (annealing)

Question 5

Types of RNA and role

Answer 5

mRNA - transcription
rRNA - ribosomal
tRNA - translation

Question 6

What is a codon? And what is an important feature.

Answer 6

mRNA strand consisting of 3 sequential nucleotides, codes for certain amino acid

Degenerate (no codon specifies more than one amino acid)

Question 7

What is a gene? Exon Vs intron?

Answer 7

Genes are stretch of nucleotides that code for a polypeptide. They determine the amino acid sequence and therefore the function of a protein.

Represents inherited unit of information.

Exons - code for protein, highly conserved
Introns - non-coding area, length outweighs exons, not well conserved between individuals spliced out during mRNA transcription

Question 8

What are chromosomes?

How many do we have (in homologous pairs)?

Names of short and long arms of chromosome?

What is the region that joins chromatids together called?

Answer 8

Linear strands of DNA that contain genes, regulatory elements and nucleotide sequences.

22 homologous autosomal pairs plus 1 pair of sex chromosomes

Short arm p, long arm q

Question 9

What are the 3 different chromasome types found in humans?

Answer 9

Metacentric (long and short arm equal in length)
Submetacentric
Acrocentric

NB telcentric and holocentric not in humans

Question 10

Describe stages of protein synthesis?

Answer 10

1. DNA transcribed to mRNA by RNA polymerase, DNA read in the 3’-5’ direction
2. mRNA translated in amino acids, requiring ribosomes

Question 11

MOA of colchicine

Answer 11

Inhibits spindle formation during metaphase, prevents microtubule assembly and thereby disrupts microtubule based inflammatory chemotaxis/generation of leukotrienes/cytokines/phagocytosis

Question 12

Name the stages of the cell cycle

Answer 12

Interphase - not part of mitosis and cell is primarily found in this stage, consists of 3 phases G1 G2 and S
Gap 1 phase
S (synthesis) phase - chromosome replication
Gap 2 phase
Mitosis

Question 13

Example of proliferation genes

Answer 13

C-myc

C-jun

Question 14

Example of inhibiting gene

Answer 14

P53

Question 15

Stem cell key characteristics

Answer 15

Capacity for self renewal over prolonged period of time
Potency - capacity to differentiate into specialised cell types
E.g. totipotent cells can differentiate into extra-embryonic cell types

Totipotent - pluripotent - multipotent - oligopotent - unipotent

Question 16

First stage of mitosis summary of events

Answer 16

Prophase - chromatids condense, centrosomes present close to nucleus, centrosome consists of pair of centrioles

Question 17

Second stage of mitosis and summary of events

Answer 17

Metaphase - nuclei disappear, nuclear membrane disintegrates, centrioles migrate to poles, mitotic spindles form, chromosomes align at metaphase plate

Question 18

Third stage of mitosis and summary of events

Answer 18

Anaphase - kinetochore (where spindle attaches to chromosome) microtubule shortens to separate chromatids

Question 19

Fourth stage of mitosis and summary of events

Answer 19

Telophase - chromosomes recondense, reformation of nuclear membrane mitosis spindles disappear, followed by cytokinesis

Question 20

Meiosis definition and product of meiosis

Answer 20

Type of cell division in which germ cells are produced with half genetic materials 4 haploid daughter cells from single diploid parent cell.

Question 21

2 stages of meiosis

Answer 21

Meiosis 1 - Separates homologous chromosomes producing 2 haploid cells
Meiosis 2 - similar to mitosis

Question 22

Stages of meiosis 1 and summary of events

Answer 22

Prophase 1 - pairing of homologous chromosomes, crossing over of chromatids at chiasma, migration of centrosome to both poles of cell

Metaphase 1 - homologous chromosome pairs align at metaphase plate

Anaphase 1 - kinetochore microtubules shorten, separating the homologous chromosomes

Question 23

Mendel’s law 2 principles

Answer 23

1. Law of segregation - each gamete receives only 1 allele for each gene
2. Law of independent assortment - alleles of different genes assort independently of one another during gametogenesis

Question 24

Models of inheritance (4 types)

Answer 24

Autosomal dominant
Autosomal recessive
X linked dominant
X linked recessive

Plus Mitochondrial

Question 25

Classification of chromosomal abnormalities

Answer 25

Aneuploidy (change in number of chromosomes)

Structural (translocation, inversion, deletion, duplication, insertion)

Question 26

Examples of aneuploidy and chromosome number

State the abnormality and the clinical example

Answer 26

Trisomy - due to non-disjunction at meiosis 1 or meiosis 2, <5% due to mosaicism

Risk increases with maternal age

NB: more extra chromosomes = greater probability of learning disability if individual survives

Down’s syndrome - trisomy 21
Edward’s syndrome - trisomy 18
Patau’s syndrome - trisomy 13

Turner’s syndrome - monopsony 45 XO
Kleinfelter’s syndrome - 47, XXY

Question 27

Clinical features of Down syndrome

Answer 27

Trisomy 21
1 in 700 live births
95% non dysjunction at meiosis
Features - raised nuchal translucency, dysmorphic features (small ears, upslanting palpebral fissures, flat facial profile, brachycephaly)
Hypotonia
Cardiac abnormalities - AV canal defect
GI - duodenal atresia, imperforate anus, hirschsprung’s
Increased risk of Alzheimer’s, AML/ALL, hypothyroidism

Cut off for invasive screening = 1:250 based on age and nuchal translucency