CHROMOSOME

BLOCK 5 MEDICAL FACULTY SRIWIJAYA UNIVERSITY

Learning Objective
MAHASISWA MAMPU MENGETAHUI APA ITU KROMOSOM, TERMASUK BAGIAN DAN FUNGSINYA MAHASISWA MAMPU MEMBEDAKAN KROMOSOM PADA SEL EUKARIOT DAN PROKARIOT MAHASISWA MAMPU MENGETAHUI KARIOTIPE PADA MANUSIA MAHASISWA MAMPU MENGETAHUI KARAKTERISTIK AUTOSOM DAN KROMOSOM SEKS MAHASISWA MAMPU MENGETAHUI ABNORMALITAS PADA KROMOSOM

KASUS
SEORANG WANITA MUDA MELAHIRKAN ANAK DENGAN DIAGNOSIS DOWN SYNDROME. SUAMI WANITA TERSEBUT YANG TELAH BERUSIA 55 TAHUN TIDAK BISA MENERIMA KENYATAAN INI DAN MENYALAHKAN ISTRINYALAH YANG MENYEBABKAN ANAKNYA MENGALAMI KELAINAN TERSEBUT. APA YANG TERJADI PADA KASUS DI ATAS

Why have to we study about chromosomes?

Can diagnose or predict genetic disorders by looking at chromosomes. This kind of analysis is used in prenatal testing and in diagnosing certain disorders, such as Down syndrome, or in diagnosing a specific type of leukemia. Such diagnosis can help patients with genetic disorders receive any medical treatment they need more quickly.

WHAT ARE CHROMOSOMES?

Chromosome Structure
Chromosomes are compact spools of DNA. Chromosome = DNA and proteins coiled together into rod-like shape Histones = proteins that help DNA stay coiled

CHROMOSOME

Chromosomes, the dark structures in this image, are copied and distributed to the daughter cells as this plant cell reproduces.

Electrone Microscope of a Chromosome

Where are the Chromosomes Stay?

You can think of chromosomes as "DNA packages" that enable all this DNA to fit in the nucleus of each cell. In the nuclei of eukaryotic cells, as they prepare to divide.. The DNA coils up and becomes denser than normal, so is more visible. WHY?

Chromosomes in Eukaryotes
Diploid: 2 of each chromosomes All human cells EXCEPT sex cells 46 chromosomes (23 pairs) in diploid cell of human 2n Haploid: Only ONE of each chromosome 23 chromosomes (NO PAIRS!!) Sex cells ONLY (sperm cells & egg cells) 1n

Chromosomes in Prokaryotes
Most prokaryotes have only one chromosome that contains all of its DNA. The chromosome here is usually circular, and is attached to the inside of the cell membrane.

Why?

Electron Micrograph = 30,000X

If you were to stretch out all the DNA from one of your cells, it would be over 3 feet (1 meter) long from end to end!

Why do chromosomes look like this?

Chromosomes are very small but can be specially prepared so we can see them using a microscope. Chromosomes taken from dividing cells are attached to a slide and stained with a dye called Giemsa. This dye gives chromosomes a striped appearance because it stains the regions of DNA that are rich in adenine (A) and thymine (T) base pairs.

PART OF CHROMOSOME
Head Telomere

Centromere Tail Telomere

All Chromosomes have telomeres at their ends (like shoelace aglets!) Telomeres have a unique DNA sequence

ttagggttagggttagggttagggttagggttaggg |||||||||||||||||||||||||||||||||||| aatcccaatcccaatcccaatcccaatcccaatccc

Head Telomere Centromere

DNA
DNA Sequence for Telomeres: ttagggttagggttaggg |||||||||||||||||| aatcccaatcccaatccc NOTICE: Tandem Repeats in Telomeres: ttagggttagggttaggg |||||||||||||||||| aatcccaatcccaatccc Repeated 800-1600 times in each Telomere

Tail Telomere

PART OF CHROMOSOME
Each 1/2 of chromosome = chromatid Centromere holds 2 chromatids together
chromatids

centromere

chromosome

What are centromeres for?

Centromeres are required for chromosome separation during cell division. The centromeres are attached to microtubules, which are proteins that can pull chromosomes toward opposite ends of each cell (the cell poles) before the cell divides. This ensures that each daughter cell will have a full set of chromosomes

 Normally, each chromosome has only one centromere. The position of the centromere relative to the end of the chromosome helps scientists tell chromosomes apart. Centromere position can be described three ways: metacentric, submetacentric or acrocentric

 In metacentric chromosomes, the centromere lies near the center of the chromosome.

 Submetacentric chromosomes have a centromere that is offcenter, so that one chromosome arm is longer than the other.

 When chromosomes are aligned, they are oriented so that the short arm, designated "p" (for petite), is at the top, and the long arm, designated "q" (simply for what follows the letter "p"), is at the bottom

Chromosome Numbers
Each species has characteristic # of chromosomes Normally, humans have 46 chromosomes in each cell; we received 23 from our mother and 23 from our father. 2 Categories Sex Chromosomes- determine gender (2) XX = female XY = male Autosomes- all other chromosomes (44- in 22 pairs)

How Do Scientists Read Chromosomes?

To "read" a set of human chromosomes, scientists first use three key features to identify their similarities and differences: Size. This is the easiest way to tell two different chromosomes apart. Banding pattern. The size and location of Giemsa bands on chromosomes make each chromosome pair unique. Centromere position. Centromeres are regions in chromosomes that appear as a constriction. They have a special role in the separation of chromosomes into daughter cells during mitosis cell division (mitosis and meiosis). Using these key features, scientists match up the 23 pairs -one set from the mother and one set from the father.

Karyotype
Chart showing all of the chromosomes present in each cell of an individual To match chromosomes, look at:
Size Banding Centromere location

From mom

Homologous pair

From dad

Homologous Pairs (Homologues)

Autosomal chromosomes in pairs
1 from mom, 1 from dad Same size, shape, and banding pattern Code for same traits
Eye color Eye color

MOM

DAD

Note: 22 autosomal homologous pairs, 2 sex chromosomes What gender is this individual?

KIND OF CHROMOSOMES

1. AUTOSOME 1. SEX CHROMOSOME

1. Autosome
Autosome: A chromosome that is not a sex chromosome. In other words, any one of the chromosomes save the sex chromosomes. People normally have 22 pairs of autosomes in every cell (together with two sex chromosomes -- an X and a Y in the male and two Xs in the female The term "autosome" was coined by Montgomery in 1906.

1. Autosome
An autosomal dominant gene is one on an autosome that is always expressed, even if a single copy exists. The chance is 1 in 2 (50%) for passing this autosomal dominant gene to a particular offspring

2. Sex Chromosomes
The nuclei of human cells contain 22 autosomes and 2 sex chromosomes. In females, the sex chromosomes are the 2 X chromosomes. Males have one X chromosome and one Y chromosome

2.1 X chromosome
The X chromosome is one of the two sex chromosomes in humans (the other is the Y chromosome). The sex chromosomes form one of the 23 pairs of human chromosomes in each cell. The X chromosome spans about 155 million base pairs (the building blocks of DNA) and represents approximately 5 percent of the total DNA in cells.

2.1 X chromosome
Each person normally has one pair of sex chromosomes in each cell. Females have two X chromosomes, while males have one X and one Y chromosome. Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in somatic cells This phenomenon is called X-inactivation or Lyonization. Xinactivation ensures that females, like males, have one functional copy of the X chromosome in each body cell.

2.1 X chromosome
The X chromosome likely contains between 900 and 1,400 genes. Genes on the X chromosome are among the estimated 20,000 to 25,000 total genes in the human genome. There are many genetic conditions related to genes on the X chromosome

2.1 X chromosome
The X chromosome carries hundreds of genes but few, if any, of these have anything to do directly with sex. However, the inheritance of these genes follows special rules. These arise because: males have only a single X chromosome almost all the genes on the X have no counterpart on the Y; thus any gene on the X, even if recessive in females, will be expressed in males.

2.2 Y Chromosome
This diagram shows the structure of the human Y chromosome. Although 95% of the Y chromosome lies between the pseudoautosomal regions, fewer than 80 genes have been found here.

2.2 Y Chromosome
The Y chromosome is one of the sexdetermining chromosomes in humans and most other mammals In humans, the Y chromosome spans 58 million base pairs (the building blocks of DNA) and represents approximately 0.38% of the total DNA in a human cell

Using Karyotypes to Predict Genetic Disorders

What happens when a person has something different, such as: Too many or too few chromosomes? Missing pieces of chromosomes? Mixed up pieces of chromosomes

Too many or too few chromosomes

To understand how our cells might end up with too many or too few chromosomes, we need to know how the cells normally get 46 chromosomes. First we need to understand meiosis. Meiosis is the cell division process that produces egg and sperm cells (gametes), which normally have 23 chromosomes each.

 If eggs and sperm only have one set of chromosomes, then how do we end up with 46 chromosomes? During fertilization, when the egg and sperm fuse, the resulting zygote has two copies of each chromosome needed for proper development, for a total of 46.

How can cells end up with too many or too few chromosomes? Some examples of genetic disorders that are caused by an abnormal number of chromosomes are: Down Syndrome Turner Syndrome Klinefelter Syndrome

 Sometimes chromosomes are incorrectly distributed into the egg or sperm cells during meiosis. When this happens, one cell may get two copies of a particular chromosome, while another cell gets none.

What happens if a sperm or egg cell with an abnormal number of chromosomes participates in fertilization? It depends on how many chromosomes the gamete has. For example, if a sperm with an extra chromosome fertilizes an egg with a normal chromosome number, the resulting zygote will have 3 copies of one chromosome. This is called trisomy (pronounced TRY-so-mi).

 If a sperm that is missing a chromosome fertilizes an egg, then the resulting zygote will have only one copy of that chromosome. This is called monosomy

 People who are born with an abnormal number of chromosomes often have genetic disorders because their cells contain too much or too little genetic information. Scientists can predict genetic disorders by looking for extra or missing chromosomes in a karyotype

Chromosomal conditions are related to the X chromosome

Klinefelter syndrome is caused by the presence of one or more extra copies of the X chromosome in a male's cells Triple X syndrome (also called 47,XXX or trisomy X) results from an extra copy of the X chromosome in each of a female's cells Turner syndrome results when each of a female's cells has one normal X chromosome and the other sex chromosome is missing or altered. other chromosomal conditions often affect sex determination

X-Inactivation
a dense, stainable structure, called a Barr body is seen in the interphase nuclei of female mammals The Barr body is one of the X chromosomes. Its compact appearance reflects its inactivity. So, the cells of females have only one functioning copy of each Xlinked gene the same as males.

X-Inactivation
X-inactivation occurs very early in embryonic development After inactivation has occurred, all the descendants of that cell will have the same chromosome inactivated. An organism whose cells vary in effective gene content and hence in the expression of a trait, is called a genetic mosaic.

X-Linkage: An Example
Hemophilia A is a blood clotting disorder caused by a mutant gene encoding the clotting factor VIII. This gene is located on the X chromosome (shown here in red). With only a single X chromosome, males who inherit the defective gene (always from their mother) will be unable to produce factor VIII and suffer from difficult-to-control episodes of bleeding

X-Linkage: An Example
In heterozygous females, the unmutated copy of the gene will provide all the factor VIII they need. Heterozygous females are called "carriers" because although they show no symptoms, they pass the gene on to approximately half their sons, who develop the disease, and half their daughters, who also become carriers.

Abnormal number (aneuploidy) of Y chromosomes

47,XYY syndrome presence of a single extra copy of the Y chromosome in each of a male's cells. Klinefelter's syndrome (47, XXY) is not an aneuploidy of the Y chromosome, but the extra X chromosome usually results in defective postnatal testicular function. This does not seem to be due to direct interference with expression of Y genes, and the mechanism is not fully understood

Chromosomal inversion
An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end to end. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself

Chromosomal inversion
Inversions are of two types: paracentric and pericentric. Paracentric inversions do not include the centromere and both breaks occur in one arm of the chromosome. Pericentric inversions include the centromere and there is a break point in each arm

Chromosomal translocation
chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. It is detected on cytogenetics or a karyotype of affected cells

Chromosomal translocation
Two main types, reciprocal (also known as nonRobertsonian) and Robertsonian. Translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced