Chromosome Karyotype and Numerical Chromosomal Abnormalities Dr

Chromosome , Karyotype and Numerical Chromosomal Abnormalities Dr. Aida Fadhel Biawi

Chromosome - what is, definition and function Chromosome is a coiled DNA molecule within the cell’s nucleus that carries an individual’s GENETIC CODE. Most of the time the chromosome’s structure is loose and indistinguishable. Only in the stage of cell division immediately before the cell divides (the metaphase) does the chromosome draw itself into a compact, rodlike structure the geneticist can see under a microscope after applying a special dye to the cell that the chromosomes absorb. It is this ability to absorb a colored dye that gives the chromosome its name, which means “colored body”.

Centromere - the position on a CHROMOSOME where the chromosome separates during cell division. The centromere is a structure of noncoding DNA) DNA that does not convey genetic information). When the cell divides the strands of the chromatids migrate in opposite directions (pull apart) at the centromere. In a photomicrograph, the centromere appears as an indented, waistlike area on the chromosome. Geneticists use the centromere’s position, along with other characteristics of the chromosome, to match chromosomes into their pairs when creating KARYOTYPES.

Telomere - definition Telomere is a structure of noncoding DNA) DNA that does not convey genetic instruction) at each end of a CHROMOSOME. Telomeres are essential for chromosome duplication during cell division. They function as handles to pull the chromatids (dividing chromosomes) apart as the mother cell divides into the two new daughter cells.

Chromosome Complements The nucleus of every diploid cell, also called a SOMATIC CELL , contains the full complement of 46 chromosomes arranged in 23 pairs. One pair contains the sex chromosomes that establish gender, paired either as XX (female) or XY (male). The other 22 pairs are autosomes. The haploid cells, the gametes (spermatozoa and OVA), contain one half the chromosome complement. When gametes merge in CONCEPTION the diploid cell they form, the ZYGOTE, acquires the full chromosomal complement. The only cells in the body that do not have chromosomes are the erythrocytes, which do not have nuclei.

Autosomes carry the bulk of genetic code. Thousands of genes line each autosome, each in its ordained position. The sex chromosomes carry several hundred genes. The GENE positions, called loci (in the singular, each position is a locus), are constant. For example, the gene loci for the ABO BLOOD TYPE are always on chromosome 9, those for the rhesus (Rh) blood type are on chromosome 1, and those for EYE color on chromosomes 15 and 19.

Chromosome Size The HUMAN GENOME PROJECT, completed in 2003, revealed the structure of chromosomes to be much larger and more complex than scientists previously had theorized. Chromosome 1, the largest CHROMOSOME, contains 2, 968 genes. The smallest chromosome, the Y chromosome, contains 231 genes.

autosome - definition Autosome is a CHROMOSOME that appears as a pair in which both chromosomes are the same in either sex, also called a nonsex chromosome. In contrast, the sex chromosomes appear as a pair that is different in males and females. The human GENOME contains 22 autosomes and one pair of sex chromosomes for a total complement of 46 chromosomes as 23 pairs.

Sex Chromosome - definition Sex Chromosome - the structure of GENETIC CODE that determines gender (male or female. (The male sex CHROMOSOME has the appearance of the letter Y and the female sex chromosome has the appearance of the letter X. A combination of XY results in male and a combination of XX results in female. The Y chromosome contains fewer than 100 genes, while the X chromosome carries several hundred genes. A number of GENETIC DISORDERS are X-linked that is, they result from mutations that occur among genes the X chromosome carries. HEMOPHILIA and some forms of MUSCULAR DYSTROPHY (notably Duchenne’s and Becker’s) are X-linked genetic disorders.

Nomenclature of chromosomes

Chromosomes in eukaryotes and prokaryotes are different PROKARYOTES EUKARYOTES single chromosome plus plasmids many chromosomes circular chromosome linear chromosomes made only of DNA made of chromatin, a nucleoprotein (DNA coiled around histone proteins) found in cytoplasm found in a nucleus copies its chromosome and divides immediately afterwards copies chromosomes, then the cell grows, then goes through mitosis to organise chromosomes in two equal groups

Organism Human Chromosome numbers 46 Chimpanzee 48 House Mouse 40 Maize 20

Karyotype - definition

Karyotype is a pictorial presentation of an individual’s chromosomes, taken from microphotographs (photographs taken through a microscope) and arranged in a numeric sequence that aligns the chromosomes from largest to smallest. This standardized presentation allows the geneticist to analyze an individual’s chromosomal profile. A geneticist can structure a karyotype from any SOMATIC CELL) non-sex cell) in the body. The most common application of karyotyping is GENETIC SCREENING of a fetus. A geneticist constructs a karyotype to evaluate whether an individual has a GENETIC DISORDER. A karyotype requires DNA from a representative cell in the body, from which the geneticist extracts and prepares the DNA for examination under the microscope.

Somatic cells used to get Karyotype : 1 - Peripheral blood 2 - Amniotic fluid 3 - Chronic Villi 4 - Tumor Cells 5 - Bone marrow cells

Amniocentesis

Chorionic villus sampling

How to get Karyotype ? ?

Final Step in Karyotype (Manual)

Human karyotype

Karyotype (by software)

Metaphase chromosomes

Karyotyped chromosomes

G-Banding Dye gives chromosomes a striped appearance because it stains the regions of DNA that are rich in adenine (A) and thymine (T) base pairs.

G-Banding • Regions that stain as dark G bands replicate late in S phase of the cell cycle and contain more condensed chromatin, • While light G bands generally replicate early in S phase, and have less condensed chromatin.

Chromosome Groups Group Chromosomes Description A 1– 3 Largest; 1 and 3 are metacentric but 2 is submetacentric B 4, 5 Large; submetacentric with two arms very different in size C 6– 12, X Medium size; submetacentric D 13– 15 Medium size; acrocentric with satellites E 16– 18 Small; 16 is metacentric but 17 and 18 are submetacentric F 19, 20 Small; metacentric G 21, 22, Y Small; acrocentric, with satellites on 21 and 22 but not on the Y Autosomes are numbered from largest to smallest, except that chromosome 21 is smaller than chromosome 22.

Fluorescence in situ Hybridization

Fluorescence in situ (Hybridization (FISH • FISH - a process which clearly paints chromosomes or portions of chromosomes with fluorescent molecules

Fluorescence in situ (Hybridization (FISH • Identifies chromosomal abnormalities • Aids in gene mapping, • analysis of chromosome structural aberrations, and ploidy determination

Detection single gene by FISH Technique Detection whole chromosome by FISH Technique

FISH - fluorescence in situ hybridisation

Detection centromeric region by FISH Technique Detection telomeric by FISH Technique

Numerical chromosomal abnormalities : 1 - Aneuploidies) --the presence of an extra chromosome (trisomy) or a missing chromosome (monosomy) -- result from segregation errors during cell division: Chromosomes do not divide evenly among daughter cells (nondisjunction) (see Fig. 2). For unknown reasons, trisomies are positively associated with advanced maternal age. . 2 - Polyploidy refers to the presence of an extra set of chromosomes. 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 recur in subsequent pregnancies. 3 - Mosaicism 4 - Chimerism

Aneuploidy as a consequence of non-disjunction

Polyploidy

Mosaicism denotes 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.

A chimera or chimaera is a single organism) usually an animal (that is composed of two or more different populations of genetically distinct cells that originated from different zygotes involved in sexual reproduction. A chimeric mouse with its offspring

Aneuploidy in Autosomes 1 - Down Syndrome (Trisomy 21) 2 - Patau Syndrome (Trisomy 13) 3 - Edward Syndrome (Trisomy 18)

Down’s Syndrome

Patau’s Syndrome

Edward’s Syndrome

Aneuploidy in Sex Chromosome 1 - Klinefilter Syndrome (47, XXY) 2 - Turner Syndrome (46, x 0 ) 3 - XYY male (Jacob’s Syndrome) 4 - Triple X female (xxx ) female.

Turners Syndrome 1 in 5, 000 births 45 chromosomes X only #23 Monosomy Nondisjunction 96 -98% do not survive to birth No menstruation No breast development Narrow hips Broad shoulders and neck

Klinefelter Syndrome 1 in 1, 100 births 47 chromosomes XXY only #23 Trisomy Nondisjunction s eard and arm b arce ingers Sc f nger Lo e teril e skin S y icat al abilit Del t men espan Low al lif Norm

Ethical Issues in Genetics and Molecular Medicine

Ethical Issues in Genetics and Molecular Medicine - the questions and concerns that arise for physicians and individuals in regard to the information GENETIC SCREENING , GENETIC TESTING , and genetic and molecular therapies. Though advances in genetics have produced significant breakthroughs in understanding, diagnosing, and sometimes treating health conditions that occur as a result of GENETIC DISORDERS , doctors and their patients grapple with the ethics of both research and therapeutics. The issues touch many of what have long been the sacred tenets of the practice of medicine: privacy, access to care, autonomy in decision making, and protection against discrimination.

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