Lecture 11 - Meiosis and chromosomal disorders.pdf

Meiosis and chromosomal disease Coley Tosto [email protected] (adapted from Dr. Amy Osborne)  Introduction  Sexual reproduction is how most multicellular organisms reproduce  Is is the fusion of two haploid cells to form a genetically recombined diploid cell  All out...

Meiosis and chromosomal disease Coley Tosto [email protected] (adapted from Dr. Amy Osborne)  Introduction  Sexual reproduction is how most multicellular organisms reproduce  Is is the fusion of two haploid cells to form a genetically recombined diploid cell  All outputs from this are genetically unique  The haploid cells are the result of meiosis  HUGE driver of variation  Errors in meiosis can lead to chromosomal disease Learning objectives  Explain the mechanisms within the meiotic process that produce genetic variation among the haploid gametes (11.1)  Describe diseases that occur due to errors in meiosis  Explain how non-disjunction leads to disorders in chromosome number  Compare disorders that aneuploidy causes  Describe how errors in chromosome structure occur through inversions and translocations (13.2) What is the point of meiosis?  Gametes – sperm and eggs (haploid, n)  Fertilized egg (zygote, diploid, 2n)  BUT! To get a zygote with the right number of chromosomes, the diploid cell has to reduce its number of chromosomes  Abnormal chromosome numbers are associated with disease  Meiosis is how we form haploid cells Meiosis  Mitosis produces diploid daughter cells  In meiosis, the daughter nuclei are haploid  There are two rounds of nuclear cell division in meiosis, meiosis I and meiosis II  The extra round of cell division creates haploid gametes that are vital for sexual reproduction  This is where most of our genetic diversity comes from. Meiosis  Chromosomes replicate themselves  Homologous chromosomes line up, either the maternal or paternal chromosome moves to the daughter cell  The chromosomes line up again, and the sister chromatids are pulled into new daughter cells, which are now haploid. Crossing over  Prophase I – homologous chromosomes pair (synapsis)  Information on the chromosomes can exchange (crossing over)  This shuffles genetic information between maternal and paternal chromosomes, introduces VARIATION Crossing over Random assortment of chromosomes  Prometaphase – paired chromosomes line up  They are orientated randomly at the equator  This process determines whether the gametes carry maternal or paternal genes for the same trait  This randomness, along with crossing over, gives each gamete a unique genetic composition Inherited disorders that arise from meiosis Chromosome identification  Cytogenetics is how we study chromosomes  Karyotypes allow us to visualise chromosomes  Chromosomes are numbered from largest to smallest  We have autosomes (Chrs. 1-22) and sex chromosomes (XX or XY)  Homologous chromosomes look the same  Chromosomes have a strict numbering/labelling system Karyotypes reveal genetic Jacobsen syndrome karyotype abnormalities chronic myelogenous leukemia karyotype Chromosome number disorders  Duplicating or losing an entire chromosome  Changes in complete sets of chromosomes  Caused by nondisjunction  Risk increases with parental age  Can occur during meiosis I or II Aneuploidy  We are (probably…) all euploids.  Aneuploidy is an error in chromosome number (e.g. monosomy, trisomy).  Monosomy is usually fatal.  Most trisomies are usually fatal too, but duplications of some smaller chromosomes (13, 15, 18, 21, 22) may survive.  Trisomy – extra ‘doses’ of genes, can affect development and body function.  Downs syndrome (trisomy 21) is the most common (viable) trisomy Sex chromosome nondisjunction in humans  Humans can function (almost) normally with abnormal numbers of sex chromosomes  X inactivation – during development, one X chromosome is always inactivated.  It compensates females for their double-dose of X chromosomes.  BUT! Even an inactive X can still express a few genes…… so extra copies can be a problem (intellectual disability, sterility) Sex chromosome nondisjunction in humans Triplo-X syndrome XXX Klinefelter syndrome XXY Turner syndrome XO Duplications and deletions Cri-du-chat – deletion of 5p Chromosomal structural rearrangements - inversions  Occur through misalignment of homologous chromosomes  Recombination of misaligned chromosomes may lead to incorrect numbers of genes on chromosomes  Effect may be mild unless they disrupt a gene sequence  May affect gene expression by moving regulators away from their gene Chromosome inversion disease  ‘Chromosome 9 inversion disorder’  Clinical significance unclear  May be associated with congenital abnormalities, growth retardation, infertility, schizophrenia Chromosomal structural rearrangements - translocations  Chromosome switching!  Can involve parts of arms or whole arms  May or may not be detrimental  Translocations occur in cancer, and schizophrenia  Translocations are usually reciprocal (no gain or loss of genetic information) Chromosomal translocation disease  Williams-Beuren syndrome  Translocation t(6;7)(p21.1;q11.23) (3Mb)  Distinctive facial features  Irises appear as stars  Intellectual disability  Friendly, gregarious, anxious  Region contains 28 genes.