Chromosomes, chromosome abnormalities and birth defects

Question 1

How are congenital defects classified?

Answer 1

Single
-Malformation
-Disruption
-Deformation
-Dysplasia
Multiple
-Sequence
-Syndrome
-Association

Question 2

Define and give an example of malformation

Answer 2

Primary structural defect
Single organ showing multifactorial inheritance
e.g. cleft lip

Question 3

Define and give an example of disruption

Answer 3

Secondary structural defect of organ/tissue
Caused by ischaemia 
NOT genetic
Extrinsic factor affects development
e.g. amniotic band = digital amputation

Question 4

Define and give an example of deformation

Answer 4

Abnormal mechanical force distorts structure
Happens later in pregnancy - organ works but has deformities
e.g. club foot

Question 5

Define and give and example of dysplasia

Answer 5

Abnormal organisation of cells within tissues

e.g. thanatophoric dysplasia

Question 6

Define and give an example of a sequence defect

Answer 6

Multiple abnormalities initiated by a primary factor
Can be genetic
e.g. Potters sequence

Question 7

Define and give an example of a syndrome

Answer 7

Consistent pattern of abnormalities with specific underlying cause
e.g. Downs syndrome

Question 8

Define and give an example of an association defect

Answer 8

Non random occurrence of abnormalities
Not explained by a syndrome
Unknown cause
e.g. VATER association

Question 9

How do non-genetic factors lead to congenital defects?

Answer 9

Problems with chromosomes

• numerical - aneuploidy
• structural
• mosaicism

Question 10

What are the 5 different types of structural problems that can occur with chromosomes?

Answer 10

Translocations
Deletions
Insertions
Inversions
Rings

Question 11

Define aneuploidy and its 4 main types

Answer 11

Loss or gain of one or more chromosomes
Monosomy - loss of 1, almost always lethal
Disomy - normal
Trisomy - gain of 1, can be tolerated by specific chromosomes
Tetrasomy - gain of 2, can be tolerated for specific chromosomes

Question 12

Define mosaicism

Answer 12

Where different cells in the same individual have different numbers or arrangements of chromosomes

Question 13

What does a normal human karyotype show?

Answer 13

46 chromosomes
22 autosomal pairs, 1 sex pair
XY males XX females

Question 14

Define chromosome translocation and its possible biological effects

Answer 14

Exchange of material between two non-homologous chromosomes
May be normal phenotype if same genes, just rearranged
Can cause gene disruption if translocation from middle or is a fusion product
Affects reproduction

Question 15

Define Robertsonian translocation

Answer 15

P lost, Q parts join on acrocentric chromosomes

occur with 13,14,15,21,22

Question 16

What 3 different chromosome aberrations lead to Down’s syndrome?

Answer 16

Trisomy 21 - non-disjunction of homologous chromosomes in meiosis 1
Robertsonian translocation - full copy of 21 attaches to a different chromosome, usually 14
Mosaicism - v rare, mix of cells with normal chromosomes and some with 47 chromosomes

Question 17

What are the main clinical features of Down’s syndrome?

Answer 17

During newborn period - hypotonia, lethargy, excess nuchal skin
Craniofacial features - macroglossia, small ears, epicanthal folds, sloping palpebral features, brushfield spots
Limbs - single palmar crease, wide gap in 1st and 2nd toes
Cardiac - septal defects, atrioventricular canal
Other - short stature, duodenal atresia
Low IQ but advanced social skills

Question 18

How does parental age affect genetic risks?

Answer 18

Increased maternal age has strong association with higher incidence of Down’s syndrome at birth

Question 19

Define non-disjunction

Answer 19

Failure of homologous or sister chromatids to separate properly during cell division

Question 20

Define copy number variant

Answer 20

Variation in the number of repeats of sections of the genome in the genome `

Question 21

Define dosage compensation

Answer 21

Process by which organisms equalise expression of genes between members of different biological sexes

Question 22

What are the 3 mechanisms of dosage compensation?

Answer 22

Random X inactivation in females
Increased X expression in males
Decreased X expression of both X chromosome genes in hermaphrodites

Question 23

Why is sex determination not solely based on sex chromosome karyotype?

Answer 23

SRY gene (testes development) can translocate to X chromosome in SRY recombination
Develop testes but are sterile because no Y so no spermatogenesis
XY females are infertile

Question 24

What is monosomy X and what does it cause?

Answer 24

Turner’s syndrome

Loss of X or Y in PATERNAL meiosis

Question 25

What are the clinical features of Turner’s syndrome?

Answer 25

Generalised oedema
Neck swelling
Webbed neck
Low set ears
Low hairline
Short stature
Diabetes and other problems

Question 26

What is Kleinfelter’s syndrome and what causes it?

Answer 26

non-dysjunction XXY
Phenotypically male
Tall with learning difficulities