MGD S11 L1 (Chromosomal Abnormalities) Part 1.pdf

University Of Basrah Ministry Of Higher Education Al-Zahraa College Of Medicine And Scientifi c Research Module: Molecule, Gene and Disease Semester: 2 Session: 11 Lecture: 19 , 20 (Part 1) Duration: 1 hr...

University Of Basrah Ministry Of Higher Education Al-Zahraa College Of Medicine And Scientifi c Research Module: Molecule, Gene and Disease Semester: 2 Session: 11 Lecture: 19 , 20 (Part 1) Duration: 1 hr Lecture Title: Chromosomal abnormalities Module staff: Dr. Farqad M. Al-Hamdani Dr. Ilham Mohamed Jawad Dr. Wameedh Hashim Alqatrani Dr. Ban M. Saleh Dr. Abeer Laily Mohammed Dr. Hamed Jaddoa Dr. Hazim T. Thwainy Dr. Shant Sunbat Dr. Zainab Muzahim Dr. Zainab Ahmad Dr. Hussein K. Abdul-Sada Dr. Myada Abd Allah Dr. Amani Niama Ass.Lect Eatidal Akram Farhan This Lecture was loaded in blackboard and you can find the material in: (Lippincott’s Illustrated Reviews: Cell and Molecular Biology Chapter 5). For more detailed instructions, any question, or you have a case you need help in, please post to the group of session  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Lecture 19, 20 Learning Outcomes: 1. Explain how the genetic information in a cell is organized as chromosomes. (LO 11.1) 2. Describe the chromosomal basis of sex determination. (LO 11.2) 3. Describe numerical and structural chromosome abnormalities and their significance. (LO 11.3)  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 1 The genetic information in a cell is organized as chromosomes  In the human cell, there are 46 chromosomes or 23 pairs (diploid number); of these 23 pairs, 22 are similar in both sexes and are called the autosomes. The remaining pair is called sex chromosomes : XX in the female cells and XY in the male cells.  The genotype is the set of genes the individual carries.  The phenotype is the external appearance of an individual as determined by his genotype.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 1  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Chromosomes LO 1  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Short arm and long arm LO 1  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 1 telocentric (not in humans) sub metacentric acrocentric metacentric  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 2 The chromosomal basis of sex determination  A sex-determination system is a biological system that determines the development of sexual characteristics in an organism. Most organisms that create their offspring using sexual reproduction have two sexes.  The XX/XY sex-determination system is the most familiar, as it is found in humans. In this system, most females have two of the same kind of sex chromosome (homogametic sex) (XX), while most males have two distinct sex chromosomes (heterogametic sex) (XY).  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research  Y-centered sex determination LO 2  The SRY gene is found on the Y chromosome ( on the P arm). The sex-determining region Y protein produced from this gene acts as a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. This protein starts processes that cause a fetus to develop male gonads (testes) and prevent the development of female reproductive structures (uterus and fallopian tubes).  Once the SRY gene is activated, cells create testosterone and anti-müllerian hormone which typically ensures the development of a single, male reproductive system. In typical XX embryos, cells secrete estrogen, which drives the body toward the female pathway.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 2 In different gonad SRY no SRY Testes Ovaries  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Chromosomal abnormalities LO 3 Chromosomal abnormalities can be classified to:  Numerical: a number of chromosomes other than 46.  Structural: physical changes to one or more of the chromosomes. 1- Numerical chromosomal abnormalities:  Ploidy _ Refers to the numbers of sets of a chromosome in a biological cell.  Euploidy _ The usual number and sets of chromosomes.  Polyploidy _The presence of three or more complete sets of chromosomes.  Aneuploidy _ The presence of additional chromosomes or missing individual chromosomes.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Types of Numerical chromosomal abnormalities: 1. Aneuploidies: the presence of an extra chromosome (trisomy) or a missing chromosome (monosomy).  It results from segregation errors during cell division: Chromosomes do not divide evenly among daughter cells (nondisjunction). For unknown reasons, trisomies are positively associated with advanced maternal age.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3 2. Polyploidy: Refers to the presence of an extra set of chromosomes. Triploidy or tetraploidy. Triploidy for example, usually occurs when 2 spermatozoa fertilize an oocyte, resulting in a zygote that contains 3 sets of chromosomes instead of 2. Numerical abnormalities are sporadic, and they do not usually Polyploidy recur in subsequent pregnancies.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 3. Mosaicism: LO 3  The presence of two or more populations of cells with different genotypes or different cell lines in one individual who has developed from a single fertilized egg. 4. Chimerism:  Is a single organism (usually an animal ) that is composed of two or more different populations of genetically distinct cells that originated from different gamete involved in sexual reproduction.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Mosaicism Vs Chimerism LO 3  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Aneuploidy in Autosomes: LO 3 1. Down syndrome (Trisomy 21) : ( 47, XY, +21)  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 2. Patau Syndrome (Trisomy13): ( 47, XX, +13) LO 3  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 3. Edward Syndrome (Trisomy 18): (47, XY, +18) LO 3  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Aneuploidy in Sex Chromosome: LO 3 (Reproductive system module) 1. Klinefilter Syndrome (47, XXY):  47 chromosomes, 23 Trisomy.  Scarce beard.  Longer fingers and arms.  Sterile.  Delicate skin.  Low mental ability.  Normal lifespan.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 2. Turner Syndrome (45, X): LO 3  45 chromosomes, 23 Monosomy.  96-98% do not survive to birth.  No menstruation.  No breast development.  Narrow hips.  Broad shoulders and neck.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 3. XYY male (Jacob’s Syndrome): LO 3 (47, XYY)  47 chromosomes, 23 Trisomy.  Normal physically.  Normal mentally.  Increase in testosterone.  More aggressive.  Norma`l lifespan.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 4. Triple X female (xxx) female: LO3 ( 47, XXX)  Normal physically.  Sometimes taller.  Normal mentally.  Increase risk of retardation.  Fertile.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Structural chromosomal abnormalities: LO 3  It results from chromosome breakage followed by reunion of the broken ends in different configurations. The environmental factors responsible for structural abnormalities are mainly:  Ionizing radiation.  Ultraviolet light.  Chemical agents.  Viral infections. Structural Abnormalities involved two main types: 1. Balanced rearrangement: The exchange or rearrangement of genetic material does not cause any missing or extra genetic material:  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3  Balanced rearrangement are generally harmless with the exception of some cases in which one of the breakpoints damages an important functional genes.  Balanced rearrangement carriers are often at risk of producing children with an unbalanced chromosomal complement. 2. Unbalanced rearrangement :  In which the chromosomal complement contains an incorrect amount of chromosomal material and usually associated with very severe clinical effects.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Types of Structural abnormalities: LO 3 1. Deletion: Loss of genetic material results in monosomy for this segment of chromosome and usually large deletion will be incompatible with survive to term.  Terminal deletion: involves a single break of the terminal part of chromosome and broken part is subsequently lost. Cri-du Chat syndrome (46,XX,5p- or 46,XY,5p-):  It results from deletion of a short arm of chromosome number 5.  The incidence 1per 20, 000 birth to 1per 50 000 birth.  Underdevelopment of larynx hence affected new born make characteristic cat like cry (Mewing cry).  Mental retardation.  Microcephaly and facial anomalies.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research Interstitial deletion: LO 3  Involves two breaks and the intervening portion of the chromosome is lost.  Some of deletion occur as micro- deletion which cannot be detected by Karyotype. It is needed FISH technique for detection, e.g.: 1. Prader-Willi: Interstitial deletion of paternal chromosome 15 (15q11–q13). 2. Angelman syndromes: Interstitial deletion of maternal chromosome 15 (15q11–q13)  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 2. Duplication: LO 3  Break and reunion of a segment of two homologous chromosomes. (Extra copies of a chromosome part) 3. Inversion: Break and inverted 180 degree, then reunited.  It involves two breaks along the chromosome in which a given segment is reversed in position. e.g.: Hemophilia.  Pericentric inversion: inverted segment involved both p & q arms with centromere.  Paracentric inversion: inverted segment involved only one arm.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3 4. Ring chromosome: Loss of telomeres or ends of both arms of chromosome and formation of a ring structure. e.g. Ring chr. 20, Ring chr. 21, Ring chr. 22, and Ring chr. X.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 5. Isochromosome: LO 3  Breakdown perpendicular at the centromere site in submetacentric chromosomes.  Creation of two non-identical chromosomes, one is a combination of the two short arms, the other a combination of the two long arms.  New chromosome in which the two arms genetically similar.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 6. Translocation: LO 3 It involves exchange of genetic material between two chromosomes, involving three types:  Reciprocal translocation: No loss of genetic material, but an exchange of genetic material between two non-homologous chromosomes to form two derivative chromosomes.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3 Balanced reciprocal translocation between a chromosome 3 and a chromosome 17 G-banding karyotype of 46, XX, t (3q;17q)  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research  Robertsonian translocation (centric fusion): LO 3  It results from break at or near the centromere in two acrocentric chromosomes (D/D, D/G, G/G) and subsequent fusion of their long arms. The fragment formed by fusion of their short arms is lost.  It is a functionally balanced translocation though chromosome number is reduced 45. Carriers are normal because of two short arms that lost do not carry important genetic material.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3 Normal Carrier G-banding karyotype of 45,XX,-14,- 21,+t(14q21q)  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research  Insertion: LO 3  No loss of genetic material, but a rearrangement of genetic material to a non-homologous chromosome.  It results from two breaks of one chromosome release a fragment and one break in another chromosome to insert this fragment.  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research LO 3 The deletions, ring chromosomes and ischromosomes are always unbalanced The inversions, insertion, reciprocal translocations and Robertsonian translocations may be balanced or unbalanced  UNIVERSITY OF BASRAH AL-ZAHRAA MEDICAL COLLEGE Ministry of higher Education and Scientific Research 12