Chromosomes, chromosome abnormalities and birth defects

Question 1

Definition of congenital abnormalities

Answer 1

Abnormalities present at birth that may be due to genetics or infection.

Question 2

Definition and example of malformation

Answer 2

Primary structural defect - atrial septal defect, cleft lip

Question 3

Definition and example of disruption

Answer 3

Secondary abnormal structure of organ or tissue - amniotic band wrapping around blood vessel cutting off blood supply to an organ

Question 4

Definition and example of deformation

Answer 4

Abnormal mechanical force distorting a structure - club foot, hp dislocation

Question 5

Definition and example of syndrome

Answer 5

Consistent pattern of abnormalities with a specific underlying cause - Down syndrome

Question 6

Definition and example of sequence

Answer 6

Multiple abnormalities initiated by primary factor - Reduced amniotic fluid leads to Potter’s sequence

Question 7

Definition and example of dysplasia

Answer 7

Abnormal organisation of cells into tissue - thanatophoric dysplasia

Question 8

Definition and example of association

Answer 8

Non-random occurrence of abnormalities not explained by syndrome. Cause usually unknown - VATER association

Question 9

Definition of teratogen

Answer 9

An agent that interferes with normal embryonic or foetal development

Question 10

Whole-chromosome factors of congenital defects

Answer 10

Numerical - loss or gain of chromosomes
Structural - Translocations, deletions, insertions, inversions
Mosaicism - Normal development of mutated chromosomes alongside normal chromosomes (stage at which mutation occurs affects degree of expression e.g. early mutation = obvious effects)

Question 11

Effect of age on genetic risk

Answer 11

Increased age of either or both parents results in increased risk of a child with genetic abnormalities

Question 12

Normal human karyotype

Answer 12

46 chromosomes in somatic cells
23 chromosomes in germ cells
Males have XY as sex-determining pair
Females have XX as sex-determining pair

Question 13

Process of chromosome banding

Answer 13

Bands labelled according to chromosome number
Short (p) or long (c) arm
Numbered out from centromere.
Used to identify different chromosomes

Question 14

Nomenclature of karyotyping

Answer 14

• Write total number of chromosomes
• Then a comma
• Then sex chromosomes
  e. g. 46,XY or 46,XX

Question 15

Definition of aneuploidy

Answer 15

An abnormality in the number of chromosomes, caused by the loss or gain of one or more chromosomes

Question 16

The 3 types of aneuploidy, their definition and whether they can be tolerated or not

Answer 16

Monosomy - loss of one chromosome, nearly always fatal
Trisomy - gain of one chromosome, can be tolerated
Tetrasomy - gain of two chromosomes, can be tolerated

Question 17

Definition of chromosome translocation

Answer 17

The transfer of genetic material from one chromosome to another when a chromosome break occurs during mitosis or meiosis

Question 18

The two types of translocation

Answer 18

Balanced

Unbalanced

Question 19

Features and consequences of balanced translocation

Answer 19

• Even exchange of genetic material between the two chromosomes
• No genetic data lost
• Chromosomes likely to remain the same length
• Little to no physiological effect seen

Question 20

Features and consequences of unbalanced translocation

Answer 20

• Uneven exchange of genetic material
• Loss or gain of genetic data
• Chromosomes unlikely to remain the same length
• More likely to cause disease

Question 21

Explain copy number variant/variation

Answer 21

• Phenomenon where sections of the genome are repeated
• Number of repeats in the genome varies between individuals
• Specifically large scale duplication or deletion events that cause variation

Question 22

Aim of meiosis

Answer 22

To create 4 haploid cells each containing 23 chromosomes

Question 23

Non-disjunction definition

Answer 23

The failure of the chromosomes to separate correctly in meiosis I or II

Question 24

Consequences of non-disjunction

Answer 24

• Creates diploid and empty germ cells
• Hence when a diploid and a haploid germ cell combine, a trisomal zygote is created, diploid-diploid = tetrasomal, haploid-empty = monosomal.

Question 25

The three chromosome aberrations that lead to Down syndrome

Answer 25

• Trisomy 21
• Robertsonian translocation
• Mosaicism

Question 26

Clinical features of Down syndrome

Answer 26

Newborn period - sever hypotonia, sleepy, excess nuchal skin
Craniofacial - macroglossia, small ears, epicanthic folds, upward sloping palpebral fissures (gaps between upper and lower eyelids)
Limbs - single palmar crease (should be 3, they have 2) wide gap between first and second toes
Cardiac - atrial and ventricular septal defects
General - Short stature, duodenal atresia (abnormal closure/absence of lumen of duodenum)
Low IQ but advanced social skills

Question 27

Dosage compensation definition

Answer 27

A genetic mechanism in which alleles of a gene automatically regulate the amount of useful product produced such that heterozygous individuals produce the same amount of product as homozygous dominant individuals.

Question 28

Mechanisms of dosage compensation

Answer 28

• One of each X chromosome in female cells is inactivated. Selection of chromosome to be inactivated is random
• Increased (2x) expression of X chromosome genes in males
• Decreased (0.5x) expression of X chromosome genes in hermaphrodites

Question 29

Mechanism of sex determination

Answer 29

The SRY gene causes development of testes. Can be translocated to X chromosome in SRY recombination.

Question 30

Consequences of SRY recombination

Answer 30

SRY gene now on X chromosome

• XX males develop testes but are sterile as other genes on Y chromosome needed for spermatogenesis
• XY females have mutations in SRY gene that lead to sterile phenotypically female individuals