Genetic Disorders

Question 1

Name the types of simple mutation

Answer 1

• Transitions(pyrimidine-to-pyrimidine and purine-to-purine)
• Transversions(pyrimidine-purine and purine-to-pyrimidine)
• Insertions and deletions(a nucleotide or a small number of nucleotides)

Question 2

What is a genetic polymorphism?

Answer 2

A genetic polymorphism can be when there are different alleles for a gene within a population:

• Does not necessarily alter the protein activity
• Natural differences in amino acids betweenindividuals

Question 3

What is a missense mutation?

Answer 3

Incorrect amino acid which may lead to malfunctioning protein

Question 4

What is a nonsense mutation?

Answer 4

STOP codon coded for meaning shortened protein

Question 5

Inherited vs sporadic mutation

Answer 5

Inherited

• Mutations are present in the germ line and somatic cells of one or both parents
• Are passed to offspring

Sporadic

• De novomutations that occur in the germ line of a parent or the newlyfertilisedegg
• Neither parent has the mutation in their somatic cells

Question 6

What are the laws of Mendelian inheritance?

Answer 6

• An individual has two genes (alleles), one from each parent
• Each allele is inherited independent of other alleles
• Recessive alleles are masked by dominant alleles
• Classification is based on how the allele is inherited and whether it masks other alleles or not
• It isnotbased on thetypeof mutation

Question 7

Autosomal dominant disorder

Answer 7

Autosomal dominant- loci on autosome, only one mutant allele needed to mask the other eg. Achondroplasia (mutation in FGFR3)

Question 8

Autosomal recessive disorder

Answer 8

loci are on autosome, both alleles need to be mutant, a carrier has one mutant and one normal eg. Hurler syndrome (MPSI, lysosomal storage disease caused by deficient IDUA, accumulated substances are heparan sulfate and dermatan sulfate, leading to developmental delay, skeletal, respiratory and cardiac abnormalities)

Question 9

X-linked recessive disorders

Answer 9

masked in females unless both are mutants, males are always affected if there is a mutant allele present eg. DMD (mutations in dystrophin Which links cytoskeleton to ECM) and Hunters (MPSII, lysosomal storage disease caused by deficient IDS, accumulated substances are heparan sulfate and dermatan sulfate, leading to developmental delay, skeletal, respiratory and cardiac abnormalities)

Question 10

X-linked dominant disorder

Answer 10

loci on X chromosome, mutant allele masks the other eg. Fragile X syndrome (caused by a CGG trinucleotide repeat expansion in the 5’ region of theFMR1gene)

Question 11

Mitochondrial genetic diseases

Answer 11

(loci on mitochondrial DNA, passed from mother to children eg. Leber hereditary optic neuropathy caused by point mutations in any of 4 genes for subunits of NADH dehydrogenase in mitochondrial DNA, leads to increased superoxide radicals in retinal ganglion cells)

Question 12

What is genomic imprinting?

Answer 12

the ability of a gene to be expressed depends uponthe sex of the parent who passed on the gene. With genomic imprinting, it is thought that the maternal or paternal imprint is erased with each succeeding generation (meiotic division). Note that the maternal/paternal imprinting is heritable through mitosis. Epigenetic factors also help establish and maintain genomic imprinting by tightly packing the chromatin – CpG hypermethylation and histone hypoacetylation.

Question 13

Prader-willi vs angelman syndrome

Answer 13

Prader-Willi Syndrome:SNRPN– thepaternalgene is normallyexpressedwhile thematernalgene issilenced.

Angelman Syndrome:UBE3A– thematernalgene is normallyexpressedwhile thepaternalgene issilenced.

In each case, the presence of asecond good copyof the gene(s) on themethylated, tightly packed copy of chromosome 15 is of no use in correcting the defect.

Question 14

Kallmanns syndrome

Answer 14

is a genetic disorder that prevents a person from starting or fully completing puberty, part of congenital hypogonadotrophic hypogonadism but also have anosmia. Underlying cause of CHH is failure in the correct production or activity of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This results in low levels of the sex hormones testosterone in males or oestrogen and progesterone in females.

Question 15

Stages of mitosis

Answer 15

1. Interphase: chromosomes are uncondensed
2. Prophase: the spindle condenses, centrioles appear and the nuclear envelope breaks down
3. Metaphase: chromosomes align
4. Anaphase: centromeres and chromatids part
5. Telophase: spindle disassembles and nuclear envelope reforms
6. Two identical diploid daughter cells (2n)

Question 16

Stages of meiosis

Answer 16

1. Prophase I (early): synapsis and crossing over occurs
2. Prophase I (late): chromosomes condense, become visible; spindle forms; nuclear envelope fragments; spindle fibres attach to chromosomes
3. Metaphase I: paired homologous chromosomes align across equator of cell
4. Anaphase I: homologous chromosomes separate to opposite poles of the cell
5. Telophase I: nuclear envelope partially assembles around chromosomes; spindle disappears, cytokinesis divides cell in two
6. Prophase II: nuclear envelope fragments; spindleforms and fibres attach to both chromosomes
7. Metaphase II: chromosomes align across equator of cell
8. Anaphase II: sister chromatids separate to opposite poles of the cell
9. Telophase II: nuclear envelopes assemble around two daughter nuclei; chromosomes decondense; spindle disappears
10. Four genetically different haploid daughter cells (1n)

Question 17

What happens in non-disjunction events?

Answer 17

• If the nondisjunction occurred in meiosis I the result is 100% abnormal cells.
• If the nondisjunction occurred in meiosis II the result is 50% abnormal cells.

Question 18

What is aneuploidy and what are the types?

Answer 18

refers to the presence of an extra chromosome or a missing chromosome, most common form of chromosomal abnormality

nullisomy (2N-2), monosomy (2N-1), trisomy (2N+1), and tetrasomy (2N+2).

Question 19

Sex chromosome vs autosomal abnormalities

Answer 19

Sex Chromosomes: 47XXY (Klinefelter syndrome) and 45X (Turner syndrome)
Autosomal: Trisomy 21 (Down syndrome)

Question 20

What is huntingtons?

Answer 20

• normal” polyglutamine (polyQ) tract (4–36 repeats) is flexible:normal polymorphism
• permits intramolecular interactions between the amino terminus of huntingtin (N17) and a carboxyl-terminal polyproline (polyP) stretch
• More than 40 repeats disrupt this interaction: full penetrance Huntington’s disease - a fatal neurodegenerative disorder