Genetic Disorders Flashcards
Name the types of simple mutation
- 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)
What is a genetic polymorphism?
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
What is a missense mutation?
Incorrect amino acid which may lead to malfunctioning protein
What is a nonsense mutation?
STOP codon coded for meaning shortened protein
Inherited vs sporadic mutation
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
What are the laws of Mendelian inheritance?
- 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
Autosomal dominant disorder
Autosomal dominant- loci on autosome, only one mutant allele needed to mask the other eg. Achondroplasia (mutation in FGFR3)
Autosomal recessive disorder
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)
X-linked recessive disorders
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)
X-linked dominant disorder
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)
Mitochondrial genetic diseases
(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)
What is genomic imprinting?
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.
Prader-willi vs angelman syndrome
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.
Kallmanns syndrome
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.
Stages of mitosis
- Interphase: chromosomes are uncondensed
- Prophase: the spindle condenses, centrioles appear and the nuclear envelope breaks down
- Metaphase: chromosomes align
- Anaphase: centromeres and chromatids part
- Telophase: spindle disassembles and nuclear envelope reforms
- Two identical diploid daughter cells (2n)
What happens in non-disjunction events?
- 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.
