Vision Collage of Medicine Year 2 Level 3 Lectures 12 & 13 PDF

CHROMOSOMES: Structure, Types and Classification by Dr.Ezat Mersal At the end of this lecture, you will be able to:- To know the definition of chromosomes. To explain the structure of the chromosome; chromatids, chromatin, centromere , satellites…. To make the differ...

CHROMOSOMES: Structure, Types and Classification by Dr.Ezat Mersal At the end of this lecture, you will be able to:- To know the definition of chromosomes. To explain the structure of the chromosome; chromatids, chromatin, centromere , satellites…. To make the difference between homologous and non homologous chromosomes. To outline the types of chromosomes. To explain the relationship between telomeres, telomerase and cancer.  The study of chromosomes and chromosomal abnormalities is referred to cytogenetic.  Human cytogenetics is a branch of genetics that is concerned with the study of human chromosomes in health & disease. Chromosomes are normally visible under a light microscope only when the cell is undergoing mitosis during metaphase. These are best seen during cell division, when the chromosomes are maximally contracted. © 2015 John Wiley & Sons, Inc. All rights reserved.  The word chromosome is derived from the Greek chroma (= color) and soma (= body).  A chromosome is a packaged and organized genetic structures containing most of the DNA of a living organism.  Chromosomes are the factors that distinguish one species from another and that enable the transmission of genetic information from one generation to the next. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  Chromosome is composed of two identical strands known as chromatids, or sister chromatids, which are the result of DNA replication taken place during the S (synthesis) phase of the cell cycle.  These sister chromatids can be seen to be joined at a primary constriction known as the centromere. © 2015 John Wiley & Sons, Inc. All rights reserved.  DNA is not usually found on its own, but rather is complexed with many structural proteins called histones as well as associated transcription factors and several other macromolecules.  This DNA and its associated proteins and macromolecules is collectively known as chromatin, which is further packaged along with its associated molecules into a discrete structure called a nucleosome.  Chromatin is present in most cells, with a few exceptions erythrocytes for example. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  Heterochromatin: More condensed Silenced genes (methylated) Gene poor (high AT content) Stains darker  Euchromatin: Less condensed Gene expressing Gene rich (higher GC content) Stains lighter © 2015 John Wiley & Sons, Inc. All rights reserved.  Telomeres – chromosome tips Repeats Act as sort of biological clock Being whittled down at each Mitosis  Centromeres – middle Highly condensed Also repetitive sequence Region where spindle fibers attach Pulling chromatids apart during Mitosis © 2015 John Wiley & Sons, Inc. All rights reserved.  Each centromere divides the chromosome into short and long arms, designated p and q respectively. © 2015 John Wiley & Sons, Inc. All rights reserved. Kinetochore: 2 disc shaped protein structure attached one on either side of the centromere. © 2015 John Wiley & Sons, Inc. All rights reserved.  b) According to position of centromere: a) According to gene complement (gene characters): 1. Metacentric: it is located in the center so, the 1. Autosomes: 22 identical pairs 2 arms are equals. that control somatic characters 2. Submetacentric: it is located midway between 2. Allosomes (heterosomes): 1 pair the center & upper end so, there is short arm that control gender (p) and long arm (q). determination. They may be 3. Acrocentric: it is very close to the upper end homologous (identical) or so, p arm is very short and q arm is very long. heterologous 4. Telocentric: it is located terminal so, no short arm. This type is not present in humans © 2015 John Wiley & Sons, Inc. All rights reserved. There are four types of chromosomes: 1. Telocentric 2. Acrocentric 3. Submetacentric 4. Metacentric Classification based on the position of the centromere © 2015 John Wiley & Sons, Inc. All rights reserved. Telocentric – no p arm; centromere is on end Acrocentric – very small p arm; centromere is very near end © 2015 John Wiley & Sons, Inc. All rights reserved.  Submetacentric – p arm just a little smaller than q arm; centromere in middle  Metacentric – p and q arms are exactly the same length; centromere in exact middle of chromosome © 2015 John Wiley & Sons, Inc. All rights reserved.  P ↑ F g i is p % Sig : sof & :? 55 Es in > I & © 2015 John Wiley & Sons, Inc. All rights reserved. 8 - => O => O 0 - © 2015 John Wiley & Sons, Inc. All rights reserved. c) According to chromosomal length: similar 1.Autosomes: Homologous 22 pairs - are numbered serially from 1-22 then classified into 7 group (A, B, C, D, E, F & G)in descending order of length. 2.Allosomes: Sex chromosomes are arranged either alone or X in group C & Y in group G. © 2015 John Wiley & Sons, Inc. All rights reserved. & - ◼ Chromosomes sometimes have stalk-like appendages called satellites. = - ◼ Satellites play a vital role in the formation of the nucleolus after cell division is completed. ◼ the nucleolus is the largest structure in the nucleus ,where it primarily serves as the site of ribosome synthesis and assembly. © 2015 John Wiley & Sons, Inc. All rights reserved.  In humans the normal cell nucleus contains 46 chromosomes, made up of 22 pairs of autosomes and a single pair of sex chromosomes  XX in the female and XY in the male.  One member of each of these pairs is derived from each parent.  Somatic cells are said to have a diploid (2n) complement of 46 chromosomes, whereas gametes (ova and sperm) have a haploid (n) complement of 23 chromosomes.  Members of a pair of chromosomes are known as homologues. © 2015 John Wiley & Sons, Inc. All rights reserved.  Homologous chromosomes: Look the same Control the same traits May code for different forms of each trait Independent origin - each one was inherited from a different parent  Non-homologous chromosomes Look different Control different traits © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  In preparation for cell division, DNA is replicated and the chromosomes condense  Each duplicated chromosome has two sister chromatids, which separate during cell division © 2015 John Wiley & Sons, Inc. All rights reserved.  Because of duplication, each condensed chromosome consists of 2 identical chromatids joined by a centromere.  Each duplicated chromosome contains 2 identical DNA molecules (unless a mutation occurred), one in each chromatid. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  Members of the same species typically have identical numbers of chromosomes in each somatic cell.  Nearly all chromosomes will exist in pairs (identical in length and centromere location) except the sex chromosomes. © 2015 John Wiley & Sons, Inc. All rights reserved. Most eukaryotes have between 10 and 50 chromosomes in their body cells. Human cells have 46 chromosomes. 23 nearly-identical pairs © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  The tip of each chromosome arm is known as the telomere.  Telomeres play a crucial role in sealing the ends of chromosomes and maintaining their structural integrity.  It allows chromosomal stability and prevent end to end fusion.  Telomeres have been highly conserved throughout evolution and in humans they consist of many tandem repeats of a TTAGGG sequence. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  During DNA replication an enzyme known as telomerase replaces the 5' end of the long strand.  Long strand would otherwise become progressively shorter until a critical length was reached when the cell could no longer divide and thus became senescent (this is in fact part of the normal cellular aging process, with most cells being unable to undergo more than 50 to 60 divisions) © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  As a cell begins to become cancerous, it divides more often and its telomeres become very short. If its telomeres get too short, the cell may die.  It can escape this fate by becoming a cancer cell and activating an enzyme called telomerase, which prevents the telomeres from getting even shorter.  Studies have found shortened telomeres in many cancers, including pancreatic, bone, prostate, bladder, lung, kidney, and head and neck. © 2015 John Wiley & Sons, Inc. All rights reserved.  isthe natural enzyme which promotes telomere repair. It is however not active in most cells. It is active in stem cells, germ cells, hair follicles and in 90 % of cancer cells.  Telomerase functions by adding bases to the ends of the telomeres.  Asa result of this telomerase activity, these cells seem to possess a kind of immortality. © 2015 John Wiley & Sons, Inc. All rights reserved.  Measuringtelomerase may be a new way to detect cancer. If scientists can learn how to stop telomerase, they might be able to fight cancer by making cancer cells age and die.  In one experiment, researchers blocked telomerase activity in human breast and prostate cancer cells growing in the laboratory, prompting the tumor cells to die. But there are risks. © 2015 John Wiley & Sons, Inc. All rights reserved.  Basic genetics : a human approach / BSCS. Dubuque, IA, Kendall/Hunt Pub. Co., c1999. 147 p. QH431.B305 1999  Genes, ethnicity, and ageing. Edited by Lincoln H. Schmitt, Leonard Freedman, Rayma Pervan. Nedlands, Australia, Centre for Human Biology, University of Western Australia ; Singapore, River Edge, NJ, World Scientific, c1995. 100 p.QH455.G45 1995  Genetic polymorphisms and susceptibility to disease. Edited by M. S. Miller and M. T. Cronin. New York, Taylor & Francis, 2000. 266 p.  GENETIC ANALYSIS AN INTEGRATED APPROACH Mark F. Sanders , John L. Bowman Second edition 2015 ISBN 978 0-321-94890-8 (student edition) www.pearsonhighered.com  Boundless Biology: Modern Understandings of Inheritance https://courses.lumenlearning.com/boundless- biology/  Anthony JF Griffiths, William M Gelbart, Jeffrey H Miller, and Richard C Lewontin (1999): modern genetic analysis