The organization of chromosomes (1).pdf

Organization of chromosomes Chromosomes The human karyotype consists of 22 pairs of non-sex chromosomes (autosomes) and two sex chromosomes, XX for females and XY for males. Each chromosome consists of a single continuous DNA strand, encoding from a few hundred to several thousand genes....

Organization of chromosomes Chromosomes The human karyotype consists of 22 pairs of non-sex chromosomes (autosomes) and two sex chromosomes, XX for females and XY for males. Each chromosome consists of a single continuous DNA strand, encoding from a few hundred to several thousand genes. Study of both normal and abnormal chromosome structure has provided valuable tools for analysis of human developmental disorders and cancer. Chromosome Structure and Analysis Chromosomes undergo a cycle of condensation and decondensation through the cell cycle. maximally decompacted during interphase achieve maximal compaction during metaphase and consists of loops of chromatin compacted by binding to condensins. The overall condensation is about 10 000- to 20 000-fold relative to the “naked” DNA double helix. Chromosomal analysis is routinely performed in medical diagnostic laboratories, where it is used to detect abnormalities of chromosome number or structure. Analysis is done on rapidly dividing cells, such as bone marrow or cancer cells, or on cells grown in culture and special staining techniques are used to reveal fine structural features of chromosomes that facilitate identification of each chromosome and reveal structural abnormalities. Chromosome Structure and Analysis Chromosomes are classified according to size and position of the centromere into a standard array referred to as the karyotype. The centromere divides most chromosomes into a long arm (designed the q arm, or “q”) and a short arm (designated the p arm, or “p”). metacentric (centromere in the center) submetacentric (centromere displaced to one end) acrocentric (centromere near one end of the chromosome). The acrocentric chromosomes are 13, 14, 15, 21, and 22. The short arms of these chromosomes consist of DNA that encodes ribosomal RNA. These regions often remain decondensed, forming stalks, with small knobs at the end referred to as satellites. Chromosome Structure and Analysis The centromeres are surrounded by blocks of highly repeated DNA sequences. A major component, the alpha-satellite DNA consists of thousands of copies of a 171bp repeat which remains highly compacted throughout the cell cycle. Chromosome Structure and Analysis The telomeres consist of 10–15 kb of a repeat unit GGGATT, with repeated sequences extending for 100–300 kb inside of this region. Chromosome Structure and Analysis Interspersed repeated sequences which are short DNA fragments that are scattered throughout the genome account for the chromosome-banding patterns obtained with special stains. SINE sequences are GC rich and tend to be found in gene-rich areas, whereas LINEs are AT rich and are found in gene-poor regions. Chromosome banding reflects differences in protein binding and chromatin condensation, which is greater in AT-rich, gene-poor regions. Molecular Cytogenetics Methods of chromosomal analysis for clinical diagnosis have evolved steadily since the 1950s. Initially it was possible to identify only gross abnormalities such as an extra or missing chromosome or major structural rearrangements. The introduction of chromosome banding in the late 1960s permitted smaller changes to be identified. Molecular tools began to be introduced that extended the resolution of detection to submicroscopic levels. Fluorescence in situ hybridization (FISH) permitted detection of deletions or duplications of about a million base pairs Techniques of comparative genomic hybridization and use of genomic microarrays have permitted detection of copy number changes down to a few hundred thousand base pairs. Molecular Cytogenetics Genomic approaches are now revealing copy number changes in individuals whose chromosomes appear entirely normal through the microscope. The high sensitivity of this approach has made it the first-line technique for diagnostic study of individuals with congenital anomalies or developmental impairment. The approach will detect unbalanced rearrangements but will miss balanced changes, making analysis with the microscope still necessary in some cases. Karyotype The complete set of chromosomes of an individual; describes the chromosome number and structure A karyogram is a written description of an organism’s chromosomes and allows determination of its karyotype Chromosomes have different lengths In human chromosomes, names are based on size (length), hence chromosome 1 is the largest chromosome By convention, chromosomes are arranged in a pattern according to size and appearance Autosomes and Sex Chromosomes Most of the chromosomes are paired based on common characteristics (length, centromere location, banding pattern, etc) Autosomes are chromosomes that are present in the same numbers in males and females Sex chromosomes are chromosomes that differ among sexes When sex chromosomes were first discovered, their function was unknown, hence designated as the X chromosome; the next ones were named Y, then Z, then W The combination of sex chromosomes within a species is associated with either male or female individuals In mammals, fruit flies and some flowering plants’ embryos those with X chromosomes are females and those with the Y are males In birds, moths and butterflies, males are ZZ and females are ZW Molecular mechanisms by which sex chromosomes determine sex differ among different organisms Sex Determination In mammals, the sex chromosomes evolved just after the divergence of the monotreme lineage from the lineage that led to placental and marsupial mammals, thus nearly all mammals use the same sex determination system During embryogenesis, the gonads will develop into either ovaries or testes. The gene TDF that is present only in Y chromosomes encodes a protein that makes the gonad mature into a testis; XX embryos do not have this gene and their gonads mature into ovaries by default Once formed, the testes begin producing sex hormones (sex steroids) that direct the rest of the embryo to become male; the ovary produce estrogens that promote female development Changes in chromosome number Aneuploidy is the addition or subtraction of a chromosome from a pair of homologs The absence of one member of a pair of homologous chromosomes is called monosomy and is indicated by 2n-1 In trisomy, there are 3 rather than the normal 2 homologs of a particular chromosome and the condition is indicated as 2n+1 Can arise from non-disjunction or the failure of at least one pair of chromosomes or chromatids to segregate during mitosis or meiosis and generate games with extra or missing chromosomes Almost always deleterious; lethal at an early stage of embryonic development Changes in chromosome number Polyploidy is the condition in which entire chromosome sets are duplicated; appears to be beneficial in some organisms especially many species of food plants Monoploids – in many species of hymenopterans (bees, wasps and ants) males are monoploid and develop from unfertilized eggs; these males do not undergo meiosis to produce gametes, instead sperm is produced after mitosis Female bees are diploid and are formed when an egg is fertilized by a sperm If an egg is not fertilized, it can still develop into a male drone This form of sex determination produces more females – worker bees, than male bees that are only needed for reproduction Haploid-diploid sex determination system Changes in chromosome number Polyploidy can be stable or sterile Stable polyploids generally have even number of copies of each chromosome (diploids 2n=2x, tetraploid 2n=4x, hexaploid 2n=6x and so on) Polyploids with an odd number of chromosomes e.g. triploids (2n=3x) tend to be sterile Many crop plants are hexaploids or octoploids Polyplod plants tend to be larger and healthier than their diploid counterparts The strawberries sold in supermarkets are octoploids (8x) strains and are much larger than those farmed using wild diploid strains Bananas, watermelons and other seedless plants are triploid; triploid banana is propagated asexually from cuttings or tissue culture while seedless watermelon is produced sexually by crossing a tetraploid watermelon with a diploid watermelon Chromosome Abnormalities Abnormalities that involve changes in a segment of a single chromosome Deletions Duplications Inversion Changes that involve 2 non-homologous chromosomes Insertion – DNA from one chromosome is moved to a non- homologous chromosome in a unidirectional manner Translocation – the transfer of chromosome segments is bidirectional and reciprocal (reciprocal translocation) Chromosome breakage occurs infrequently as a result of physical damage (e.g. by ionizing radiation), movements of some types of transposons and other factors During the repair of a broken chromosome, deletions, insertions, translocations and even inversions can be introduced Organellar genomes DNA in Chloroplast Mitochondrial DNA Often present in multiple copies within each organelle In most sexually reproducing species, organellar chromosomes are inherited only from only one parent, usually the one that produces the largest gamete. Thus is mammals, angiosperms and many other organisms, mitochondria and chloroplasts are maternally-inherited These organelles are likely the remnants of prokaryotic endosymbionts that entered the cytoplasm of ancient progenitors of present day eukaryotes (endosymbiont theory) Organellar genomes do not undergo mitosis and meiosis