Genomics and Personalized Medicine
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What is the main difference between mitosis and meiosis in terms of the number of cells produced?

  • Mitosis produces 4 cells, while meiosis produces 2 cells
  • Mitosis produces 1 cell, while meiosis produces 2 cells
  • Mitosis produces 2 cells, while meiosis produces 4 cells (correct)
  • Mitosis produces 1 cell, while meiosis produces 1 cell

    • During which stage of mitosis do chromosomes line up at the centre of the spindle?

  • Telophase
  • Metaphase (correct)
  • Prophase
  • Anaphase

    • What is the term for the process of DNA exchange between homologous chromosomes during prophase I of meiosis?

  • Chiasmata
  • Genetic drift
  • Synapsis
  • Crossing over (correct)

    • What is the ploidy of the cells produced during meiosis?

    <p>Haploid (n)</p> Signup and view all the answers

    During which stage of mitosis do sister chromatids separate to opposite poles of the cell?

    <p>Anaphase</p> Signup and view all the answers

    What is the location of the alpha globin gene?

    <p>16p13.3</p> Signup and view all the answers

    What is the primary reason for genotyping of variants in personalized medicine?

    <p>To determine the individual's response to a particular drug</p> Signup and view all the answers

    What is the structure formed when an octamer of histones binds to DNA?

    <p>Nucleosome</p> Signup and view all the answers

    What is the term for the study of the genetic component of a cell through the visualization and analysis of chromosomes?

    <p>Cytogenetics</p> Signup and view all the answers

    What is the characteristic of chromosomes after DNA replication?

    <p>They consist of two identical chromatids linked together at the centromere</p> Signup and view all the answers

    What is the term for the protein that links nucleosomes together?

    <p>H1</p> Signup and view all the answers

    What is the purpose of G-banding in cytogenetics?

    <p>To visualize and analyze chromosomes</p> Signup and view all the answers

    What is the normal karyotype of a male?

    <p>46 XY</p> Signup and view all the answers

    What is the location of the centromere in a chromosome?

    <p>In the middle of the chromosome</p> Signup and view all the answers

    What is the result of meiosis in terms of the number of cells?

    <p>4 cells in total</p> Signup and view all the answers

    What is the purpose of X-chromosome dosage compensation?

    <p>To prevent female cells from having double the amount of X-linked genes being active</p> Signup and view all the answers

    What determines the male sex in biological sex determination?

    <p>The presence of Y chromosome</p> Signup and view all the answers

    What is the term for an irregular number of chromosomes?

    <p>Aneuploidy</p> Signup and view all the answers

    Which of the following trisomies can lead to live births?

    <p>Trisomy 13</p> Signup and view all the answers

    What is the purpose of amniocentesis?

    <p>To check for chromosomal abnormalities</p> Signup and view all the answers

    What is the risk of having a child with Down syndrome at maternal age of 43?

    <p>1:50</p> Signup and view all the answers

    Why are 95% of aneuploid conceptions due to non-disjunction during oogenesis?

    <p>Because oocytes are suspended after first cell division</p> Signup and view all the answers

    What is the term for an inherited disorder linked to a variation of a single gene?

    <p>Monogenic disorder</p> Signup and view all the answers

    What is the symbol for a female in a pedigree diagram?

    <p>Circle</p> Signup and view all the answers

    In an autosomal recessive inheritance, what is the probability of a child being a carrier of the disease if both parents are carriers?

    <p>50%</p> Signup and view all the answers

    What is the consequence of inheriting a single mutant allele of the CFTR gene?

    <p>The individual is a carrier of the disease but does not develop cystic fibrosis</p> Signup and view all the answers

    What is the characteristic of an autosomal recessive disease?

    <p>The disease affects both males and females equally</p> Signup and view all the answers

    What is the term for the normal functional allele of the CFTR gene?

    <p>Wildtype allele</p> Signup and view all the answers

    What is the consequence of inheriting two mutant alleles of the CFTR gene?

    <p>The individual develops cystic fibrosis</p> Signup and view all the answers

    What is the function of the CFTR protein in normal cells?

    <p>It pumps Cl- out of cells</p> Signup and view all the answers

    What is the characteristic of an autosomal dominant inheritance?

    <p>The disease is frequent in the pedigree</p> Signup and view all the answers

    What is the probability of a child developing cystic fibrosis if both parents are carriers of the mutant allele?

    <p>25%</p> Signup and view all the answers

    What is the term for the sequence variation of a gene?

    <p>Allele</p> Signup and view all the answers

    What is the characteristic of a consanguineous marriage?

    <p>The couple is related by blood</p> Signup and view all the answers

    What is the characteristic of a trait that has an autosomal dominant inheritance pattern?

    <p>A single copy of the mutant allele is enough to cause the disease.</p> Signup and view all the answers

    What is the result of the expansion of the polyglutamine region in the huntingtin protein in Huntington's disease?

    <p>A gain of negative function of the mutant protein.</p> Signup and view all the answers

    What is the genotype of an individual with a normal phenotype in Huntington's disease?

    <p>HH</p> Signup and view all the answers

    What is the typical ratio of progeny from an unaffected individual and a heterozygote affected individual in Huntington's disease?

    <p>2 normal and 2 Huntington's disease</p> Signup and view all the answers

    What is the alternative explanation for dominant inheritance in other syndromes?

    <p>Somatic second hit</p> Signup and view all the answers

    What is the characteristic of a trait that has an X-linked recessive inheritance pattern?

    <p>The trait skips a generation.</p> Signup and view all the answers

    What is the genotype of a female carrier of the haemophilia A mutation?

    <p>Hh</p> Signup and view all the answers

    What is the result of the mutation in the factor VIII gene in haemophilia A?

    <p>A decrease in the activity of the factor VIII protein.</p> Signup and view all the answers

    What is the characteristic of a parent of an individual with haemophilia A?

    <p>The parent is a carrier of the mutation.</p> Signup and view all the answers

    What is the inheritance pattern of haemophilia A?

    <p>X-linked recessive</p> Signup and view all the answers

    Study Notes

    Warfarin and Personalized Medicine

    • Normal dose of anti-coagulant drug warfarin can lead to excessive bleeding
    • Genotyping of variants can be useful in therapy, especially in personalized medicine, which involves prescribing drugs based on an individual's genotype

    DNA Packaging

    • DNA is packaged in the nucleus with positively charged histone proteins
    • DNA + histones = chromatin
    • Octamer of histones (2x H2A, H2B, H3, H4) forms a core with DNA around the outside, called a nucleosome
    • Histone H1 links nucleosomes together
    • Nucleosomes form a chromatin fiber, which loops out of a central nuclear matrix protein to create individual chromosomes

    Human Karyotype

    • Human cells have 46 chromosomes (23 from each parent), making them diploid (2n)
    • There are 22 pairs of autosomes and 1 pair of sex chromosomes
    • Staining chromosomes at Metaphase with Giemsa dye produces alternating light and dark bands, characteristic of each chromosome
    • Normal female karyotype is 46 XX, and normal male karyotype is 46 XY
    • Chromosome 1 is the largest, and chromosome 22 is the smallest

    Organisation of Chromosomes

    • After DNA replication, each chromosome consists of two identical chromatids linked together at the centromere
    • The arms of the chromosomes are often different lengths, with a short (p) and long (q) arm
    • The location of genes can be specified based on the G-banding pattern and the arm of the chromosome, e.g., alpha globin genes: 16p13.3

    Mitosis

    • Mitosis produces 2 cells with 46 chromosomes (diploid: 2n) that are genetically identical
    • Involves one round of DNA replication and one round of chromosomal segregation
    • DNA is replicated, and chromosomes are duplicated to create chromatids in prophase
    • Chromosomes line up at the center of the spindle in metaphase
    • Chromatids are separated to the poles of the cell in anaphase
    • Nuclear membrane reforms, and the cell splits in two

    Meiosis

    • Meiosis produces 4 cells with 23 chromosomes (haploid: n) that are genetically variable
    • Involves one round of DNA replication and two rounds of chromosomal segregation
    • Steps of meiosis:
      1. Homologous pairs of chromosomes line up and DNA is exchanged by crossing over in prophase I
      2. Homologous pairs of chromosomes line up at the center of the spindle in metaphase I
      3. Chromosomes are separated to the poles of the cell in anaphase I
      4. Sister chromatids stay together; nuclear membrane reforms, and the cell splits in two
      5. Chromosomes line up at the center of the spindle in metaphase II
      6. Chromatids are separated to the poles of the cell in anaphase II
      7. Nuclear membrane reforms, and each cell splits in two – 4 cells in total (n)

    X-Chromosome Dosage Compensation

    • Genes from both maternal and paternal inherited chromosomes are usually active
    • To prevent female cells from having double the amount of X-linked genes being active, there is a mechanism of X-chromosome dosage compensation
    • Female cells are 46 XX, but only one of the X chromosomes is active
    • This means that, with respect to X-linked genes, the level of expression is identical in male and female cells
    • Early in embryology, one of the X chromosomes is inactivated randomly, and a gene on the X-chromosome is transcribed as Xist ncRNA, which triggers the transcriptional silencing of one of the X-chromosomes

    Biological Sex Determination

    • The presence of the Y chromosome determines the male sex
    • Extremely rare mutations have identified the region of the Y chromosome responsible for male sex determination
    • Males with 46 XX karyotype may have a translocation of part of the Y to the X chromosome
    • Females with a 46 XY karyotype may have a deletion of part of the Y chromosome
    • Identification of the SRY gene, which encodes a protein that acts as a testis-determining factor (TDF)

    Abnormal Karyotypes

    • A complete set of chromosomes is called euploidy, and an irregular number is called aneuploidy
    • Aneuploidies are caused by the failure of homologous chromosomes to separate properly during meiosis, known as non-disjunction
    • Responsible for 50% of spontaneous abortions, frequently caused by trisomies (3 copies of a chromosome)
    • The only trisomies that lead to live births are:
      • Trisomy 13 (Patau syndrome): 47 XX +13 or 47 XY +13
      • Trisomy 18 (Edward's syndrome): 47 XX +18 or 47 XY +18
      • Trisomy 21 (Down syndrome): 47 XX +21 or 47 XY +21

    Karyotype Determination

    • Amniocentesis is carried out during weeks 15-20 of pregnancy to check for chromosomal abnormalities
    • Removal of amniotic fluid, isolation of fetal cells, and quantification of chromosomes
    • Risk of having a child with Down syndrome increases from 1:600 at maternal age of 33 to 1:50 at maternal age of 43
    • 95% of aneuploid conceptions are due to non-disjunction during oogenesis

    Monogenic Disorders

    • A single gene variant (mutant) is linked to an inherited disorder
    • Modes of inheritance:
      • Autosomal recessive
      • Autosomal dominant
      • X-linked (recessive)

    Cystic Fibrosis

    • Caused by a mutation of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene
    • Locus of the gene is on chromosome 7
    • An individual inherits one version of the CFTR gene from each parent
    • Sequence variation of a gene is called an allele
    • Genome contains extensive gene polymorphism; some of these alleles are non-functional and are called mutant alleles or mutants
    • For individuals to develop CF, they must inherit a mutant allele from both parents – it is an autosomal recessive disease

    Autosomal Dominant

    • Trait is frequent in pedigree
    • Individuals are affected in each generation
    • Trait affects males and females equally
    • Trait is transmitted by either sex
    • Parents of individual with phenotype also have the phenotype

    Huntington's Disease

    • Neurodegenerative disease; gradual cognitive decline
    • Caused by mutations at the HD locus
    • Normal HD gene has ~28 repeats of the CAG sequence in the gene
    • Mutant HD gene has > 36 repeats of the CAG sequence
    • This expansion of the polyglutamine region produces a version of the huntingtin protein that aggregates and is neurotoxic
    • The inheritance of the disease is autosomal dominant

    X-Linked Recessive Inheritance

    • Trait is rare in pedigree
    • Trait skips a generation
    • Trait most frequently in males
    • Fathers cannot transmit it to their sons
    • Parents of affected individuals do not have the disease

    Haemophilia A

    • Haemophilia A is a blood clotting disorder and is due to a mutation in the factor VIII gene on the X chromosome
    • It has X-linked recessive inheritance
    • Female carriers of the mutation have 50% of the normal activity of factor VIII and this is sufficient to maintain normal blood clotting function

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    Description

    This quiz covers the basics of genomics, including DNA packaging and genotyping, as well as its application to personalized medicine and drug therapy.

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