GENETIC ABNORMALITIES

Question 1

List the 4 main types of human genetic disorders.

Answer 1

Chromosome disorders
Single gene disorders
Mitochondrial disorders
Multifactorial disorders

Question 2

Describe chromosome disorders. Give examples.

Answer 2

Entire chromosomes, or large segments of chromosomes are altered.
Aneuploidy: missing or extra chromosomes.
Monosomy: only 1 copy of a chromosome.
Trisomy: having 3 copies of a chromosome.
Down Syndrome: trisomy 21
XXY = Kleinfelters syndrome
X = Turners syndrome
Edwards syndrome: trisomy 18
Patau Syndrome: trisomy 13

Question 3

Describe single gene disorders.

Answer 3

Single genes are altered, for example by a single nucleotide “point” mutation, or by multi nucleotide changes.

Question 4

Describe mitochondrial disorders.

Answer 4

Changes in mitochondrial DNA. Can be important, but has relatively few genes.

Question 5

Describe multifactorial disorders.

Answer 5

Includes multiple gene defects, or multiple gene involvement plus environmental factors.

Question 6

Describe Down Syndrome.

Answer 6

Trisomy 21 (autosomal disorder).
Characteristic symptoms include cognitive retardation, palmer crease, epicanthal fold.
Can arise from non-disjunction of chromosomes during meiosis (egg has an extra copy of chromosome 21) in which sister chromatids did not disjoin and migrate to separate poles, but instead stayed together.

Question 7

Give an example of a sex chromosome disorder.

Answer 7

Turners Syndrome. Complete absence of one X chromosome, or partial deletion of X chromosome.
Symptoms include growth and mental retardation, infertility and increased cancer rates.

Question 8

Describe Klinefelter Syndrome.

Answer 8

47XXY. Presence of an extra X chromosome in a male. Symptoms can include above average height, small testes, low testosterone, usually sterile, little body hair and usually have normal intelligence but may have learning or behavioural difficulties.
Breast development may occur with an increased risk of breast cancer.

Question 9

What are the 2 types of chromosomal aberrations?

Answer 9

Numerical and structural.
Numerical aberrations include trisomy, monosomy and triploidy (2 sperm fertilise 1 egg).
Structural aberrations include translocations and deletions. They may be balanced, in which there is no loss or gain of chromosomal content, or be unbalanced.

Question 10

What is mosaicism?

Answer 10

Occurs when not all cells show the same genotype.

Question 11

What are the 3 types of balanced structural aberrations?

Answer 11

Translocation: part of one chromosome breaks off and rejoins on another chromosome.
Reciprocal translocation: parts of 2 chromosomes swap places
Inversion: one chromosome breaks in 2 places, and the resulting segment is re-inserted in the wrong orientation.
Balanced abnormalities often present without obvious clinical symptoms, but greatly increase the chances of replication errors which may lead to more severe chromosomal disorders in children.

Question 12

Describe the 3 types of unbalanced structural aberrations.

Answer 12

Deletions: part of one chromosome is deleted. Usually occurs de novo and is not passed on.
Duplications: part of the chromosome is duplicated either within the same chromosome or by attachment or insertion into a different chromosome.
Other: various other unbalanced abnormalities occur including ring chromosomes.

Question 13

Describe Fluorescent In Situ Hybridisation (FISH).

Answer 13

FISH uses different coloured fluorescently labelled probes to recognise each chromosome. FISH makes it easier to detect small chromosomal abnormalities that would traditionally need an expert to find using traditional stains.

Question 14

Define haploinsufficiency.

Answer 14

When one copy of a chromosome (haploid) or chromosomal locus is insufficient to maintain function, and clinical symptoms result.
Usually occurs with larger deletions causing more severe phenotypes.

Question 15

Describe an example of a micro deletion.

Answer 15

Smith-Magenis Syndrome. Microdeletion on chromosome 17. Symptoms include mental retardation, dysmorphic features, hyperactivity and self-destructive behaviour.

Question 16

Describe single nucleotide mutations.

Answer 16

Most common form of single gene disorder is point mutation. Point mutations are reffered to as a single nucleotide polymorphism (SNP) if it occurs at a frequency of more than 1% in a population.
Many SNPs are harmless, but others may cause disease and may be lethal.

Question 17

How may a harmful mutation survive within a population?

Answer 17

If it does not have a harmful effect until later in life (giving carriers time to reproduce), or the mutation may have beneficial effects in some circumstances but harmful effects in others (e.g. sickle cell anaemia protects against malaria).

Question 18

Give an example of how a single nucleotide change can re-shape the human phenotype.

Answer 18

Testicular Feminism Syndrome. X-linked recessive disorder in which there is an insensitivity to adrogens. Single nucleotide change in the androgen receptor means all cells are insensitive to male hormones, and secondary male characteristics do not develop, leading to a female phenotype.

Question 19

Give an example of a single gene disorder involving mutinucleotide mutations.

Answer 19

Huntington’s Disease is a triplet repeat disorder causing fatal autosomal dominant adult onset brain degenerative disease.
Involves excessive numbers of repeated sets of three nucleotide bases within affected genes.
Symptoms include uncontrollable movements, cognitive impairment with psychiatric disturbances (hostility, anger, aggression, depression).

Question 20

How do triplet repeat disorders arise?

Answer 20

“Slippage” of DNA polymerase causes increasing numbers of repeats with each round of DNA synthesis, which can disrupt the function of a gene. The number of repeats must usually exceed a threshold before disease occurs.
Repeat number tends to increase with each generation, leading to greater severity of symptoms and earlier onset of disease (AKA anticipation).

Question 21

Discuss the importance of repeat number in Huntington’s Disease.

Answer 21

Everyone has a few CAG repeats in the Huntington gene, but people with the disease generally have over 40 repeats.
The more repeats the more abnormal the protein product and usually, the more severe the symptoms, and earlier the onset of disease.

Question 22

Give an example of a multifactorial genetic condition.

Answer 22

Xeroderma Pigmentosum.

Question 23

Describe Xeroderma Pigmentosum.

Answer 23

Multifactorial genetic disorder. Occurs in 1:30000. If children with the disorder are exposed to UV radiation, they develop melanomas and die at an early age. If they are protected from UV radiation however, they can lead a relatively normal, healthy life.

Question 24

Give an example of a multifactorial disorder (threshold trait).

Answer 24

Cleft palate or lips. The expression of a group of under active genes must exceed a threshold in order for the malformation to occur. The further the threshold is exceeded, the greater the extent of the malformation.
Cleft palate is a congenital malformation which is inherited as a multifactorial trait.

Question 25

define epistasis.

Answer 25

genetic variance due to non-additive effects at different loci.

Question 26

Compare single gene disorders with multifactorial disorders.

Answer 26

Single gene disorders are often easily fitted to Mendelian models (autosomal dominant/recessive or sex linked).
Multifactorial disorders can involve complex interactive effects such as gene-gene interactions, epistasis, gene-environment interactions, and their inheritance patterns are often not clear cut.

Question 27

Describe familial diseases.

Answer 27

Family history is a clear risk factor for the disease. Mutant genes are usually rare in the general population. Having mutation is associated with high disease risk.
environmental influence generally unimportant due to the strong effects of mutant gene.