genetic bases of disease Flashcards
What are alleles
different variations of the same gene that impart the same characteristic
What is Mendel’s Law of Segregation (4)
- characteristics can have alternate versions - alleles
- each characteristic has 2 alleles
- dominant allele is expressed
- 2 alleles for each characteristic segregate during gamete production
What is the centromere and telomere
Centromere – the constriction point in the chromosome
Telomere – tips of chromosome
What are the types of chromosomes (4)
- Metacentric - centromere in centre
- submetacentric - centromere near the middle
- acrocentric - centromere near the end of chromosome
- telocentric - centromere at the end of the chromosome
What is the difference between haploid and diploid (4)
- Haploid = 1 copy of each chromosome
- Diploid = 2 copies of each chromosome
- Somatic cells = diploid
- Gametes = haploid
What happens during mitosis (4)
- Generating diploid cells
- Prophase - duplicated chromosomes (two sister chromatids)
- Metaphase - chromosomes align at the metaphase plate
- anaphase telophase - sister chromatids separate during anaphase
What happens during meiosis (7)
- Generating haploid sex cells
- Parent cell chromosome duplicates
- prophase - Tetrad formed by synapsis of homologous chromosomes
- metaphase - tetrads align at the metaphase plate
- anaphase telophase - homologous chromosomes separate; sister chromatids remain together
- anaphase ii - no further duplication; sister chromatids separate
- Results in genetic variation
What is the importance of meiosis (4)
- Germ-line cells (diploid) produce gametes (haploid)
- Produces genetic variation among offspring (evolutionary adaptation) via:
- Independent segregation of homologous chromosomes
- Recombination of homologous chromosomes by crossing over
What are types of point mutations (3)
- Substitution - base replaced with another
- Insertions - information added to genome
- Deletions - information removed from the genome
What are outcomes of point mutations (4)
- No change in sequence
- Missense sequence - amino acid changed, non-functional protein
- Nonsense sequence - no protein
- Rearranged sequence - non-functional protein
What are single nucleotide polymorphisms (SNPs) (3)
- difference in a single nucleotide
- most common type of genetic variation among people (DNA polymorphism)
- most SNPs have no effect on health or development but are useful
What can single nucleotide polymorphisms be used for (3)
- predict an individual’s response to certain drugs
- track the inheritance of disease genes within families
- associated with complex diseases such as heart disease, diabetes, and cancer
What are the main types of genetic disorders (4)
- Single gene (Mendelian/monogenic)
- Multiple gene (complex/polygenic)
- Chromosomal
- Mitochondrial
What are classifications of single gene disorders (5)
- Autosomal dominant - Huntington’s
- Autosomal recessive - Cystic fibrosis, sickle cell anaemia
- X-linked dominant
- X-linked recessive - haemophilia, G6PD deficiency
- Y-linked - male infertility
What causes Huntington’s disease (3)
- A triplet repeat expansion (CAG = glutamine)
- in the Huntingtin gene (chromosome 4)
- Severity related to size of expansion
What causes Cystic fibrosis
Mutation in the CFTR (Cystic Fibrosis Transmembrane Regulator) gene
How do X-linked dominant gene disorders work (2)
- Affected females will have a 50-100% chance that their child will inherit the disorder
- Affected males will have normal sons and affected daughters
How do X-linked recessive gene disorders work (2)
- Affected males will have normal sons and carrier daughters
- Affected females will have a 50% chance that their child inherits the disorder (sons only) or is a carrier (daughter)
What are Y-linked gene disorders (4)
- Only affects males
- Usually results in infertility, so rarely passed on
- The Y chromosome is relatively small and contains very few genes
- there are relatively few Y‐linked disorders
What are multiple gene disorders (4)
- Changes/mutations in multiple genes
- probably associated by varying environmental factors
- Hard to establish a clear-cut inheritance pattern
- e.g. heart disease, Alzheimer’s, arthritis, cancers, obesity, autism, hypertension, cleft palate…
What are chromosomal disorders (3)
- Changes that affect the entire chromosome.
- Can be structural alterations or changes in number of the chromosomes
- These changes are usually not inherited but occur during the formation of reproductive cells
What are the types of chromosomal disorders (2)
- Sex chromosomal disorders
- Autosomal chromosomal disorders
What are the types of sex chromosomal disorders (4)
- Turners syndrome (XO, monosomy X) - female, minor, infertile
- Triple-X syndrome (XXX) - female, infertile, reduced mental acuity
- Klinefelter’s syndrome (XXY, XXXY) - male, low testosterone, female features, sterile
- Jacob’s syndrome (XYY) - male, acne, v tall, aggressive
What are autosomal chromosomal disorders (3)
- Down’s syndrome
- Edward’s syndrome
- Patou syndrome
What happens in Down’s syndrome (3)
- Extra chromosome 21.
- mental retardation
- characteristic physical appearance
What happens in Edward’s syndrome (3)
- Trisomy of chromosome 18.
- More severe than Down’s
- most foetuses don’t survive
What happens in Patou syndrome (4)
- Extra chromosome 13.
- Very severe
- mental disorder
- physical defects resulting in death as babies.
What are mitochondrial genetic disorders (2)
- Heteroplasmy – cells contain varying numbers of mtDNA (some may have mutations others don’t)
- Leber’s Hereditary Optic Neuropathy (LHON)
Results in loss of vision due to degradation of optic nerve
What is gene therapy (6)
- Treatment of a disease, that is caused by an absent or abnormal gene
- Gene(s) can be replaced, altered or supplemented.
- Genetic disease can be caused by single or multiple genetic components
- Human Genome Project – sequenced the entire human genetic makeup
- Pharmacogenetics/pharmacogenomics – study of the genetic bases of variation in patients responses to drugs
- Personalised medicines
How are genes used as drugs ex vivo (4)
- A therapeutic gene is inserted into a specifically engineered virus
- cells from the target tissue are removed from the patient
- the cells are grown in large numbers in tissue culture plates. The cultured cells are then mixed with the virus.
- the cells are then returned to the patient to replace the function lost due to the inheritance of mutant gene(s).
What must be considered when using genes as drugs (5)
- Identify the genetic component of the disease
- Therapeutic gene’s desired effect
- Local/systemic treatment?
- Duration of therapeutic gene expression
- Route of administration
What is somatic gene therapy (2)
- Insertion of genetic material into diploid cells where the therapeutic gene is not passed on to offspring
- No change in the genetic profile is passed on
What is germ-line gene therapy (4)
- treatment of unborn ‘patients’.
- Manipulation of genes in gamete cells.
- Permanent cures to hereditary disorders
- Ethical issues raised
What are the main categories of gene delivery vectors (2)
- Viral vectors
- Non-viral systems
What diseases are targeted with gene therapy (2)
- Single gene disorders - Cystic F, ADA, SCID, familial hypercholesterolemia
- multifactorial genetic disorders - cancer, atherosclerosis, diabetes mellitus
