Lecture 1

Question 1

What are the three types of chromosomes?

Answer 1

metacentric
submetacentric
acrocentric

Question 2

List the main types of congenital abnormalities

Answer 2

malformation - primary structural defect, single organ e.g. cleft

deformation- abnormal force distorted the structure e.g. club foot

disruption - secondary structural defect e.g. amniotic band causing an amputation

dysplasia - abnormal cell organisation e.g. FGFR3 mutation

syndrome - consistent pattern of abnormalities with a specific underlying cause e.g. Down’s

association - non random occurrence of abnormalities e.g. VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal and limb abnormalities)

sequence - multiple abnormalities that are caused by a primary factor e.g. reduced amniotic fluid (oligohydroamnios) causes Potter’s

Question 3

What are the three main types of chromosomal abnormalities?

Answer 3

numerical

structural - translocation, deletions, insertions

mocaicism - different cell lineages resulting in a mixture of normal and abnormal. Severity depends on when the mitotic division occurred

Question 4

What is meiosis non-dysjunction and the effects of it?

Answer 4

When the chromosomes fail to separate during meiosis and this results in a gamete having an extra chromosome or no chromosome
This can lead to aneuploidy (monosomy or trisomy)

Question 5

Give an example of monosomy, the features and causes

Answer 5

Turner’s syndrome
Short 4th metacarpals, webbed neck, aorta defects, short, ovarian failure and infertility

Causes: loss of X/Y during meiosis, single arm deletion, mocaicism, ring chromosome (breaks in the end of two arms and the sticky ends join but some fragments are lost, they are unstable during mitosis and so mocaicism occurs)

Question 6

Give an example of polysomy and its features

Answer 6

Klinefelter’s syndrome
- clumsiness, verbal learning difficulties, tall, gynaecomastia, infertility, risk of leg ulcers, osteoporosis and breast carcinoma

Question 7

What is the p arm and q arm?

Answer 7

p -short

q - long

Question 8

How do we name genes on a chromosome?

Answer 8

Name the chromosome number, then the arm then the band (band can be seen under the microscope + SPECIAL STAINS)

e.g. 7q22

Question 9

What is copy number variant?

Answer 9

Some sections in the genome are repeated and the no of repeats varies in the population. Eg the CAG repeat in Huntingtin gene

Question 10

What are translocations?

Answer 10

Re arrangements between parts of chromosomes. Balanced and unbalanced (partial anueploidy) exist

Question 11

What happens to someone with a balanced translocation during meiosis?

Answer 11

Their chromosomes form quadravalents during meiosis instead of bivalents and this can result in strange genetic exchanges resulting in disease.

Question 12

Give an example of trisomy 18

Answer 12

Edward’s syndrome

- heart defects, kidney malformation digestive tract defects and mental retardation

Question 13

Give an example of trisomy 13

Answer 13

Patau’s syndrome

- heart defects, mental retardation and holoprosencephaly

Question 14

What is a genomic disorder?

Answer 14

caused by loss/gain of DNA

Question 15

Give examples of genomic disorders

Answer 15

Cri du Chats - microcephaly,epicanthal folds, low set ears, hypotonia, sever psychomotor and mental retardation
DELETION on 5p

Charcot-Marie-Tooth disease type 1A DUPLICATION

Di George’s syndrome
congenital heart disease, palatal abnormalities, learning difficulties
DELETION on 22q

Question 16

Down’s syndrome - causes and features

Answer 16

1 in 700 births
causes: trisomy 21, robertsonian translocation (breakage of acrocentric chromosomes 12,14,15,21,22 at centomere are fusion of q arms) and mocaicism (non dysjunction in mitosis in zygote)

features:
Newborn period - severe hypotonia, sleepy, excess nuchal skin

Craniofacial - macroglossia (large tongue), small ears, epicanthic folds (eye folds), upward sloping palpebral fissues (eye folds), Brushfield spots (spots in the iris)

Limbs - single palmar crease, wide gap between first and second toes (sandal gap)

Cardiac - Atrial and Ventricular septal defects

Other - short statue, duodenal atresia (narrowing)

Question 17

Di George syndrome cause and clinical presentations

Answer 17

Cardiac abnormalities
Abnormal facies- low ears and wide spaced eyes 
Thymic Hypoplasia 
Cleft palate
Hypocalcaemia (parathyroid hypoplasia) 

CATCH 22
caused by micro deletion on 22q (q arm on Chr22)

Question 18

Charcot marie tooth disease 1a cause and presentations

Answer 18

Foot drop (muscle weakness leading to can't lift the front part of feet and toes) + Foot deformities (arched foot)
Distal muscle wasting/weakness
Absent reflexes
Lack of sensation in upper/lower limbs
Slow nerve conduction velocity

FAS-L Die 17
caused by micro-DUPLICATION 17p (chr17, short arm)