LECTURE 1 Human Chromosomes Human Karyotype, Slides of Cell Biology

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LECTURE 1

Human Chromosomes

Human Karyotype

M. Faiyaz-Ul-Haque, PhD, FRCPath

Lecture Objectives:

By the end of this lecture, the students should be

able to:

 Describe the number, structure, and

classification of human chromosomes.

 Explain what a Karyotype is and how it is

obtained.

 Describe chromosomal banding and explain its

use.

Describe the process of in situ hybridization and the

information it provides

Definitions:

Cytogenetics:

The study of the structure and function of chromosomes and

chromosome behaviour during somatic and germline division

Molecular genetics:

The study of the structure and function of genes at a molecular

level and how the genes are transferred from generation to

generation.

Cytogenesis

Human Cytogenetics involves the study of human chromosomes in health

and disease.

Chromosome studies are an important laboratory diagnostic procedure in

1. prenatal diagnosis : diagnosis before birth in order to determine whether the fetus has a genetic abnormality. It can be done by by studying the chromosome of a sample.

2. certain patients with mental retardation and multiple birth defects : it caused of abnormal chromosome e.g. Huntington's disease

3. patients with abnormal sexual development : caused by abnormal sexual chromosome e.g. Klinefelter's syndrome.

4. some cases of infertility or multiple miscarriages

5. in the study and treatment of patients with malignancies & hematologic disorders e.g. Leukemia

New techniques allow for increased resolution.

CHROMOSOMES:

■ carry genetic material.

■ heredity: each pair of homologues consists of one paternal and one

maternal chromosome.

■ The intact set is passed to each daughter cell at every mitosis.

■ only seen by E.M. (Electronic Microscope)

Structure of Chromosomes :

it is always colling and folding.

Primary coiling : DNA double helix

Secondary coiling : around histones (basic

proteins)nucleosomes. That means DNA + histones =

nucleosomes

Tertiary coiling  chromatin fiber. That means many

nucleosomes form chromatin fiber.

Chromatin fibers form long loops on non-histone proteins tighter

coils  chromosome That means chromatin fiber+ colling on non-

histone proteins= chromosome.

Histone protein

DNA

Nucleosome

(secondary coiling)

In what Phase do we study chromosomes? Methaphase

How do we stop the division at metaphase? we use colchicine: to cut the bindles (spinal fibers) so that the division would stop.

we can see DNA in White blood cells but not in red blood cells because RBCs

don’t have nucleus.

The 2 sister-chromatids are principally held together at the centromeric region.

Each chromosome has a centromere (CEN),

region which contains the kinetochore,

CEN divides the chromosome into two arms: the short arm (p arm) and the long arm (q arm).

■ Each arm terminates in a telomere.

Metaphase chromosomes

Chromosomal classification:

• 22 pairs of autosomes, numbered from 1 to 22 by

order of decreasing length

• 1 pair of sex chromosomes:

XX in the female,

XY in the male.

Karyotyping based on

Size

Position of the centromere

the presence or absence of satellites.

Normal Karyotypes

46,XY  male

46,XX  female

Abnormal Karyotypes

47, XY, + 21 : addition of one chromosome ( down syndrome)

45, XY, t (D;G) : translocation between group G and D

( cut of the two centromers two chromosomes join together becoming one  the

result is loss of a chromosome. ) NO REDUCTION

Chromosomes are divided into 7 groups (A, B , C, D, E, F, G, X ) based on their size, position of centromere, the presence or absence of satellites

Types of Banding

G Banding:

Treat with trypsin and then with Geimsa Stain.

Trypsin " which is a digestive fluid that digest the chromosomes.

R Banding

Heat and then treat with Geimsa Stain. Reverses G-banding , e.g. the dark band in G- banding is a light one in R- banding. It ’ s made to confirm the banding pattern

Q Banding:

Treat with Quinicrine dye giving rise to fluorescent bands. It requires an ultraviolet fluorescent microscope

C Banding:

Staining of the Centromere. Treat with acid followed by alkali prior to G banding

The most popular

In situ hybridization: The use of a DNA or RNA probe to detect complementary genetic material in cells or tissue. In situ hybridization involves hybridizing a labeled nucleic acid to suitably prepared cells or tissues on microscope slides to allow visualization in situ (in the normal location).