CHROMOSOMECHROMOSOME

BLOCK 5BLOCK 5

MEDICAL FACULTY MEDICAL FACULTY SRIWIJAYA UNIVERSITYSRIWIJAYA UNIVERSITY

Learning ObjectiveLearning Objective MAHASISWA MAMPU MENGETAHUI APA ITU MAHASISWA MAMPU MENGETAHUI APA ITU

KROMOSOM, TERMASUK BAGIAN DAN KROMOSOM, TERMASUK BAGIAN DAN FUNGSINYAFUNGSINYA

MAHASISWA MAMPU MEMBEDAKAN MAHASISWA MAMPU MEMBEDAKAN KROMOSOM PADA SEL EUKARIOT DAN KROMOSOM PADA SEL EUKARIOT DAN PROKARIOTPROKARIOT

MAHASISWA MAMPU MENGETAHUI MAHASISWA MAMPU MENGETAHUI KARIOTIPE PADA MANUSIAKARIOTIPE PADA MANUSIA

MAHASISWA MAMPU MENGETAHUI MAHASISWA MAMPU MENGETAHUI KARAKTERISTIK AUTOSOM DAN KROMOSOM KARAKTERISTIK AUTOSOM DAN KROMOSOM SEKSSEKS

MAHASISWA MAMPU MENGETAHUI MAHASISWA MAMPU MENGETAHUI ABNORMALITAS PADA KROMOSOMABNORMALITAS PADA KROMOSOM

KASUSKASUS

SEORANG WANITA MUDA MELAHIRKAN ANAK SEORANG WANITA MUDA MELAHIRKAN ANAK DENGAN DIAGNOSIS DOWN SYNDROME. DENGAN DIAGNOSIS DOWN SYNDROME.

SUAMI WANITA TERSEBUT YANG TELAH SUAMI WANITA TERSEBUT YANG TELAH BERUSIA 55 TAHUN TIDAK BISA MENERIMA BERUSIA 55 TAHUN TIDAK BISA MENERIMA KENYATAAN INI DAN MENYALAHKAN KENYATAAN INI DAN MENYALAHKAN ISTRINYALAH YANG MENYEBABKAN ISTRINYALAH YANG MENYEBABKAN ANAKNYA MENGALAMI KELAINAN TERSEBUT.ANAKNYA MENGALAMI KELAINAN TERSEBUT.

APA YANG TERJADI PADA KASUS DI ATASAPA YANG TERJADI PADA KASUS DI ATAS

Why have to we study about Why have to we study about chromosomes?chromosomes?

Can diagnose or predict genetic disorders by Can diagnose or predict genetic disorders by looking at chromosomes. looking at chromosomes.

This kind of analysis is used in prenatal testing This kind of analysis is used in prenatal testing and in diagnosing certain disorders, such as and in diagnosing certain disorders, such as Down syndrome, or in diagnosing a specific type Down syndrome, or in diagnosing a specific type of leukemia. of leukemia.

Such diagnosis can help patients with genetic Such diagnosis can help patients with genetic disorders receive any medical treatment they disorders receive any medical treatment they need more quickly.need more quickly.

WHAT ARE CHROMOSOMES?WHAT ARE CHROMOSOMES?

Chromosome StructureChromosome Structure

Chromosomes are compact spools of DNA.Chromosomes are compact spools of DNA.

Chromosome = DNA and proteins coiled Chromosome = DNA and proteins coiled together into “rod-like” shapetogether into “rod-like” shape

Histones = proteins that help DNA stay Histones = proteins that help DNA stay coiled coiled

CHROMOSOMECHROMOSOME

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

Electrone Microscope of a ChromosomeElectrone Microscope of a Chromosome

Where are the Chromosomes Stay?Where are the Chromosomes Stay? You can think of You can think of

chromosomes as "DNA chromosomes as "DNA packages" that enable packages" that enable all this DNA to fit in the all this DNA to fit in the nucleus of each cell. nucleus of each cell.

In the nuclei of In the nuclei of eukaryotic cells, as they eukaryotic cells, as they prepare to divide..prepare to divide..

The DNA coils up and The DNA coils up and becomes denser than becomes denser than normal, so is more normal, so is more visiblevisible. . WHY?WHY?

Chromosomes in EukaryotesChromosomes in Eukaryotes

Diploid:Diploid:– 2 of each 2 of each

chromosomeschromosomes– All human cells All human cells

EXCEPT sex cellsEXCEPT sex cells– 46 chromosomes (23 46 chromosomes (23

pairs) in diploid cell of pairs) in diploid cell of humanhuman

– 2n2n

Haploid:Haploid:– Only ONE of each Only ONE of each

chromosomechromosome– 23 chromosomes (NO 23 chromosomes (NO

PAIRS!!)PAIRS!!)– Sex cells ONLY Sex cells ONLY

(sperm cells & egg (sperm cells & egg cells)cells)

– 1n1n

Chromosomes in ProkaryotesChromosomes in Prokaryotes

Most prokaryotes have only one Most prokaryotes have only one chromosome that contains all of its DNA.chromosome that contains all of its DNA.

The chromosome here is usually circular, The chromosome here is usually circular, and is attached to the inside of the cell and is attached to the inside of the cell membrane.membrane.

Why?Why?

Electron Micrograph = Electron Micrograph = 30,000X30,000X

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

end!end!

Why do chromosomes look like Why do chromosomes look like this?this?

Chromosomes are very small but can be specially Chromosomes are very small but can be specially prepared so we can see them using a microscope. prepared so we can see them using a microscope.

Chromosomes taken from dividing cells are Chromosomes taken from dividing cells are attached to a slide and stained with a dye called attached to a slide and stained with a dye called Giemsa.Giemsa.

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

PART OF CHROMOSOMEPART OF CHROMOSOME

All Chromosomes have All Chromosomes have telomerestelomeres at their at their endsends(like shoelace aglets!)(like shoelace aglets!)

HeadTelomere

Centromere

TailTelomere TelomeresTelomeres have a have a

unique DNA unique DNA sequence…sequence…

ttagggttagggttagggttagggttagggttaggg…||||||||||||||||||||||||||||||||||||aatcccaatcccaatcccaatcccaatcccaatccc…

DNADNADNA Sequence for DNA Sequence for

TelomeresTelomeres::ttagggttagggttaggg…ttagggttagggttaggg…||||||||||||||||||||||||||||||||||||aatcccaatcccaatccc…aatcccaatcccaatccc…

HeadTelomere

Centromere

TailTelomere

NOTICE:NOTICE:Tandem RepeatsTandem Repeats in in

Telomeres:Telomeres:ttagggttagggttagggttagggttagggttaggg……||||||||||||||||||||||||||||||||||||aatcccaatcccaatcccaatcccaatcccaatccc……Repeated 800-1600 timesRepeated 800-1600 times

in each Telomerein each Telomere

PART OF CHROMOSOMEPART OF CHROMOSOME

Each 1/2 of chromosome = chromatidEach 1/2 of chromosome = chromatid Centromere holds 2 chromatids togetherCentromere holds 2 chromatids together

centromere

chromatids

chromosome

What are centromeres for?What are centromeres for?

Centromeres are required for Centromeres are required for chromosome separation during cell chromosome separation during cell division. division.

The centromeres are attached to The centromeres are attached to microtubules, which are proteins microtubules, which are proteins that can pull chromosomes toward that can pull chromosomes toward opposite ends of each cell (the cell opposite ends of each cell (the cell poles) before the cell divides. poles) before the cell divides.

This ensures that each daughter This ensures that each daughter cell will have a full set of cell will have a full set of chromosomes chromosomes

Normally, each chromosome has only one Normally, each chromosome has only one centromere.centromere.

The position of the centromere relative to The position of the centromere relative to the end of the chromosome helps the end of the chromosome helps scientists tell chromosomes apart. scientists tell chromosomes apart.

Centromere position can be described Centromere position can be described three ways: metacentric, submetacentric three ways: metacentric, submetacentric or acrocentric or acrocentric

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

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

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

Chromosome NumbersChromosome Numbers

Each species has characteristic # of chromosomesEach species has characteristic # of chromosomes Normally, humans have 46 chromosomes in each Normally, humans have 46 chromosomes in each

cell; we received 23 from our mother and 23 from cell; we received 23 from our mother and 23 from our father.our father.

2 Categories2 Categories– Sex Chromosomes- determine gender (2)Sex Chromosomes- determine gender (2)

XX = female XY = maleXX = female XY = male– Autosomes- all other chromosomes (44- in 22 Autosomes- all other chromosomes (44- in 22

pairs)pairs)

How Do Scientists Read How Do Scientists Read Chromosomes?Chromosomes?

To "read" a set of human chromosomes, scientists first use To "read" a set of human chromosomes, scientists first use three key features to identify their similarities and three key features to identify their similarities and differences:differences:

SizeSize. This is the easiest way to tell two different . This is the easiest way to tell two different chromosomes apart. chromosomes apart.

Banding patternBanding pattern. The size and location of Giemsa . The size and location of Giemsa bands on chromosomes make each chromosome pair bands on chromosomes make each chromosome pair unique. unique.

Centromere positionCentromere position. Centromeres are regions in . Centromeres are regions in chromosomes that appear as a constriction. They have a chromosomes that appear as a constriction. They have a special role in the separation of chromosomes into special role in the separation of chromosomes into daughter cells during mitosis cell division (mitosis and daughter cells during mitosis cell division (mitosis and meiosis). meiosis).

Using these key features, scientists match up the 23 pairs -- Using these key features, scientists match up the 23 pairs -- one set from the mother and one set from the father.one set from the mother and one set from the father.

KaryotypeKaryotype

Chart showing all of the chromosomes Chart showing all of the chromosomes present in each cell of an individualpresent in each cell of an individual

To match chromosomes, look at:To match chromosomes, look at:– SizeSize– Banding Banding – Centromere locationCentromere location

Homologous pairFrom mom From dad

Homologous Pairs (Homologous Pairs (HomologuesHomologues))

Autosomal chromosomes in pairsAutosomal chromosomes in pairs– 1 from mom, 1 from dad1 from mom, 1 from dad– Same size, shape, and banding patternSame size, shape, and banding pattern– Code for same traits Code for same traits

Eye color

MOM DAD

Eye color

Note: 22 autosomal homologous pairs, 2 sex chromosomes

What gender is this individual?

KIND OF CHROMOSOMESKIND OF CHROMOSOMES

1.1. AUTOSOMEAUTOSOME

2.2. SEX CHROMOSOMESEX CHROMOSOME

1. Autosome1. Autosome

Autosome:Autosome: A chromosome that is not a sex A chromosome that is not a sex chromosome. chromosome.

In other words, any one of the chromosomes save In other words, any one of the chromosomes save the sex chromosomes. the sex chromosomes.

People normally have 22 pairs of autosomes in every People normally have 22 pairs of autosomes in every cell (together with two sex chromosomes -- an X and cell (together with two sex chromosomes -- an X and a Y in the male and two Xs in the female a Y in the male and two Xs in the female

The term "autosome" was coined by Montgomery in The term "autosome" was coined by Montgomery in 1906.1906.

1. Autosome1. Autosome

An An autosomal dominant geneautosomal dominant gene is one on an is one on an autosome that is always expressed, even if autosome that is always expressed, even if a single copy exists. a single copy exists.

The chance is 1 in 2 (50%) for passing this The chance is 1 in 2 (50%) for passing this autosomal dominant geneautosomal dominant gene to a particular to a particular offspring offspring

2. Sex Chromosomes 2. Sex Chromosomes

The nuclei of human cells The nuclei of human cells contain 22 autosomes and 2 contain 22 autosomes and 2 sex chromosomes. sex chromosomes.

In females, the sex In females, the sex chromosomes are the 2 chromosomes are the 2 X X chromosomeschromosomes. .

Males have one X Males have one X chromosome and one chromosome and one Y Y chromosomechromosome

2.1 X chromosome 2.1 X chromosome

The X chromosome is one of the two sex The X chromosome is one of the two sex chromosomes in humans (the other is the Y chromosomes in humans (the other is the Y chromosome). chromosome).

The sex chromosomes form one of the 23 pairs of The sex chromosomes form one of the 23 pairs of human chromosomes in each cell. human chromosomes in each cell.

The X chromosome spans about 155 million base The X chromosome spans about 155 million base pairs (the building blocks of DNA) and represents pairs (the building blocks of DNA) and represents approximately 5 percent of the total DNA in cells.approximately 5 percent of the total DNA in cells.

2.1 X chromosome2.1 X chromosome

Each person normally has one pair of sex chromosomes in Each person normally has one pair of sex chromosomes in each cell. each cell.

Females have two X chromosomes, while males have one Females have two X chromosomes, while males have one X and one Y chromosome. X and one Y chromosome.

Early in embryonic development in females, one of the two Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated X chromosomes is randomly and permanently inactivated in somatic cells in somatic cells

This phenomenon is called X-inactivation or Lyonization. X-This phenomenon is called X-inactivation or Lyonization. X-inactivation ensures that females, like males, have one inactivation ensures that females, like males, have one functional copy of the X chromosome in each body cell. functional copy of the X chromosome in each body cell.

2.1 X chromosome2.1 X chromosome

The X chromosome likely contains between The X chromosome likely contains between 900 and 1,400 genes.900 and 1,400 genes.

Genes on the X chromosome are among the Genes on the X chromosome are among the estimated 20,000 to 25,000 total genes in estimated 20,000 to 25,000 total genes in the human genome.the human genome.

There are many genetic conditions related There are many genetic conditions related to genes on the X chromosometo genes on the X chromosome

2.1 X chromosome2.1 X chromosome

The X chromosome carries hundreds of genes but The X chromosome carries hundreds of genes but few, if any, of these have anything to do directly few, if any, of these have anything to do directly with sex. However, the inheritance of these genes with sex. However, the inheritance of these genes follows special rules. follows special rules.

These arise because: These arise because: males have only a single X chromosome males have only a single X chromosome almost all the genes on the X have no counterpart almost all the genes on the X have no counterpart

on the Y; thus on the Y; thus any gene on the X, any gene on the X, even if recessive in femaleseven if recessive in females, ,

will be expressed in males. will be expressed in males.

2.2 Y Chromosome 2.2 Y Chromosome

This diagram shows the This diagram shows the structure of the human Y structure of the human Y chromosome.chromosome.

Although 95% of the Y Although 95% of the Y chromosome lies between the chromosome lies between the pseudoautosomal regions, pseudoautosomal regions, fewer than 80 genes have fewer than 80 genes have been found here. been found here.

2.2 Y Chromosome2.2 Y Chromosome

The The Y chromosomeY chromosome is one of the sex- is one of the sex-determining chromosomes in humans and determining chromosomes in humans and most other mammals most other mammals

In humans, the Y chromosome spans 58 In humans, the Y chromosome spans 58 million base pairs (the building blocks of million base pairs (the building blocks of DNA) and represents approximately 0.38% DNA) and represents approximately 0.38% of the total DNA in a human cell of the total DNA in a human cell

Using Karyotypes to Predict Using Karyotypes to Predict Genetic DisordersGenetic Disorders

What happens when a person has something What happens when a person has something different, such as:different, such as:

Too many or too few chromosomes? Too many or too few chromosomes? Missing pieces of chromosomes? Missing pieces of chromosomes? Mixed up pieces of chromosomes Mixed up pieces of chromosomes

Too many or too few Too many or too few chromosomeschromosomes

To understand how our cells might end up with too To understand how our cells might end up with too many or too few chromosomes, we need to know many or too few chromosomes, we need to know how the cells normally get 46 chromosomes.how the cells normally get 46 chromosomes.

First we need to understand meiosis. Meiosis is First we need to understand meiosis. Meiosis is the cell division process that produces egg and the cell division process that produces egg and sperm cells (gametes), which normally have 23 sperm cells (gametes), which normally have 23 chromosomes each. chromosomes each.

If eggs and sperm only have one set of If eggs and sperm only have one set of chromosomes, then how do we end up with chromosomes, then how do we end up with 46 chromosomes? 46 chromosomes?

During fertilization, when the egg and sperm During fertilization, when the egg and sperm fuse, the resulting zygote has two copies of fuse, the resulting zygote has two copies of each chromosome needed for proper each chromosome needed for proper development, for a total of 46.development, for a total of 46.

How can cells end up with too many or too How can cells end up with too many or too few chromosomes?few chromosomes?

Some examples of genetic disorders that Some examples of genetic disorders that are caused by an abnormal number of are caused by an abnormal number of chromosomes are:chromosomes are:

Down Syndrome Down Syndrome Turner Syndrome Turner Syndrome Klinefelter Syndrome Klinefelter Syndrome

Sometimes chromosomes are incorrectly Sometimes chromosomes are incorrectly distributed into the egg or sperm cells distributed into the egg or sperm cells during meiosis. during meiosis.

When this happens, one cell may get two When this happens, one cell may get two copies of a particular chromosome, while copies of a particular chromosome, while another cell gets none. another cell gets none.

It depends on how many chromosomes the It depends on how many chromosomes the gamete has. gamete has.

For example, if a sperm with an extra chromosome For example, if a sperm with an extra chromosome fertilizes an egg with a normal chromosome fertilizes an egg with a normal chromosome number, the resulting zygote will have 3 copies of number, the resulting zygote will have 3 copies of one chromosome. one chromosome.

This is called trisomy (pronounced TRY-so-mi).This is called trisomy (pronounced TRY-so-mi).

What happens if a sperm or egg cell with an What happens if a sperm or egg cell with an abnormal number of chromosomes participates in abnormal number of chromosomes participates in

fertilization?fertilization?

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

This is called monosomyThis is called monosomy

People who are born with an abnormal People who are born with an abnormal number of chromosomes often have genetic number of chromosomes often have genetic disorders because their cells contain too disorders because their cells contain too much or too little genetic information. much or too little genetic information.

Scientists can predict genetic disorders by Scientists can predict genetic disorders by looking for extra or missing chromosomes in looking for extra or missing chromosomes in a karyotype a karyotype

Chromosomal conditions are related to the X Chromosomal conditions are related to the X

chromosomechromosome

Klinefelter syndrome is caused by the presence of one or Klinefelter syndrome is caused by the presence of one or more extra copies of the X chromosome in a male's cells more extra copies of the X chromosome in a male's cells

Triple X syndrome (also called 47,XXX or trisomy X) Triple X syndrome (also called 47,XXX or trisomy X) results from an extra copy of the X chromosome in each results from an extra copy of the X chromosome in each of a female's cells of a female's cells

Turner syndrome results when 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 has one normal X chromosome and the other sex chromosome is missing or altered. chromosome is missing or altered.

other chromosomal conditions often affect sex other chromosomal conditions often affect sex determination determination

X-Inactivation X-Inactivation

a dense, stainable structure, called a dense, stainable structure, called a a Barr bodyBarr body is seen in the is seen in the interphase nuclei of female interphase nuclei of female mammals mammals

The Barr body is one of the X The Barr body is one of the X chromosomes. Its compact chromosomes. Its compact appearance reflects its inactivity. appearance reflects its inactivity.

So, the cells of females have only So, the cells of females have only one functioning copy of each X-one functioning copy of each X-linked gene — the same as males. linked gene — the same as males.

X-Inactivation X-Inactivation

X-inactivation occurs very early in X-inactivation occurs very early in embryonic development embryonic development

After inactivation has occurred, all After inactivation has occurred, all the descendants of that cell will the descendants of that cell will have the same chromosome have the same chromosome inactivated. inactivated.

An organism whose cells vary in An organism whose cells vary in effective gene content and hence effective gene content and hence in the expression of a trait, is called in the expression of a trait, is called a a genetic mosaicgenetic mosaic. .

X-Linkage: An Example X-Linkage: An Example

Hemophilia AHemophilia A is a blood clotting disorder caused is a blood clotting disorder caused by a mutant gene encoding the clotting by a mutant gene encoding the clotting factor VIIIfactor VIII. .

This gene is located on the X chromosome (shown This gene is located on the X chromosome (shown here in red). here in red).

With only a single X chromosome, males who With only a single X chromosome, males who inherit the defective gene (always from their inherit the defective gene (always from their mother) will be unable to produce factor VIII and mother) will be unable to produce factor VIII and suffer from difficult-to-control episodes of bleedingsuffer from difficult-to-control episodes of bleeding

X-Linkage: An Example X-Linkage: An Example

In heterozygous females, the unmutated copy of In heterozygous females, the unmutated copy of the gene will provide all the factor VIII they need. the gene will provide all the factor VIII they need.

Heterozygous females are called Heterozygous females are called "carriers""carriers" because although they show no symptoms, they because although they show no symptoms, they pass the gene on to approximately half their sons, pass the gene on to approximately half their sons, who develop the disease, and half their daughters, who develop the disease, and half their daughters, who also become carriers. who also become carriers.

47,XYY syndrome 47,XYY syndrome presence of a single extra presence of a single extra copy of the Y chromosome in each of a male's copy of the Y chromosome in each of a male's cells. cells.

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

Abnormal number (aneuploidy) of Y Abnormal number (aneuploidy) of Y

chromosomeschromosomes

Chromosomal inversion Chromosomal inversion

An An inversioninversion is a is a chromosome rearrangement chromosome rearrangement in which a segment of a in which a segment of a chromosome is reversed chromosome is reversed end to end. end to end.

An inversion occurs when a An inversion occurs when a single chromosome single chromosome undergoes breakage and undergoes breakage and rearrangement within itself rearrangement within itself

Chromosomal inversion Chromosomal inversion

Inversions are of two types: Inversions are of two types: paracentricparacentric and and pericentricpericentric. .

Paracentric inversions do not Paracentric inversions do not include the centromere and include the centromere and both breaks occur in one arm of both breaks occur in one arm of the chromosome. the chromosome.

Pericentric inversions include Pericentric inversions include the centromere and there is a the centromere and there is a break point in each arm break point in each arm

Chromosomal translocationChromosomal translocation

chromosome translocationchromosome translocation is is a chromosome abnormality a chromosome abnormality caused by rearrangement of caused by rearrangement of parts between nonhomologous parts between nonhomologous chromosomes. chromosomes.

It is detected on cytogenetics or It is detected on cytogenetics or a karyotype of affected cells a karyotype of affected cells

Chromosomal translocationChromosomal translocation

Two main types, Two main types, reciprocalreciprocal (also known as non-(also known as non-Robertsonian) and Robertsonian) and RobertsonianRobertsonian. .

Translocations can be Translocations can be balancedbalanced (in an even (in an even exchange of material with no exchange of material with no genetic information extra or genetic information extra or missing, and ideally full missing, and ideally full functionality) or functionality) or unbalancedunbalanced