Chapter 8

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Chapter 8

The Human Karyotype and Chromosome Behavior

8.1 The Human Karyotype

Standard Karyotypes

Dosage Compensation of X-linked Genes

The Calico Cat is a Result of X-Chromosome Inactivation

Pseudoautosomal Inheritance

Gene Content and Evolution of the Y Chromosome

The term karyotype refers to a display of the chromosomes of a cell by lining them up, beginning with the largest chromosome and with the short arm of the chromosome oriented toward the top of the karyotype sheet.

Chromosomes used for karyotypes are taken from cells that are in the metaphase stage of mitosis. Chromosomes at metaphase of mitosis are in the most condensed state.

Figure 8.2 is an example of a karyotype of a normal human male. Blood cells arrested in metaphase were stained with Giemsa and photographed with a microscope.

The chromosomes were then cut out of the photograph and paired with their homolog from biggest homolog to smallest homolog.

Giemsa is a stain that stains chromosomal DNA. Giemsa stains A-T rich areas of a chromosome more intensely than G-C rich areas of a chromosome.

Therefore, chromosomes will contain dark-staining and light-staining bands when stained with Giemsa.

The banding pattern is unique for a given chromosome and can be used to identify a specific chromosome.

Figure 8.3 Designations of the bands and interbands in a human karyotype.

Types of chromosomes.

Metacentric – Metacentric chromosomes have the centromere located near the middle so there are equal sized p and q arms. An example is chromosome 1.

Submetacentric - Submetacentric chromosomes have the centromere located slightly off center so the q arm is slightly longer than the p arm. An example is chromosome 4.

Acrocentric – Acrocentric chromosomes have their centromeres very near one end so there is not much of a p arm. An example is chromosome 21.

Figure 8.5 Shapes of the three different types of chromosomes during anaphase.

Human ancestors had 48 chromosomes rather than 46. In the evolution of the human genome it is thought that two acrocentric chromosomes fused to create human chromosome 2.

Figure 8.6 Human ancestors had 48 pairs of chromosomes rather 46.

The fusion of two non-homologous acrocentric chromosomes is called a Robertsonian translocation.

Figure 8.26 Formation of a Robertsonian translocaton.

The following is a list of karyotype symbols used in human genetics.

1-22 - Autosome designations

X, Y - Sex chromosome designations

p - Short arm of the chromosome

q -long arm of the chromosome

del - part of a chromosome has been deleted

dup - part of a chromosome has been duplicated

t – part of a chromosome has been translocated to another chromosome.

Karyotype symbols continued.

+ or - These symbols represent addition (+) or loss (-) of an entire chromosome. For example, +21 denotes an extra chromosome 21, as in Down Syndrome.

If these symbols are placed after the chromosome number, they indicate an increase or decrease in the length of the chromosome part. For example, 5p- indicates loss of part of the short arm of chromosome 5, as in cri du chat syndrome.

Karyotype formulas

A karyotype formula begins with the total number of chromosomes in the cell followed by the sex chromosomes (first X’s and then the Y’s).

For example, the formula for a normal male is 46,XY.

The formula for a normal female is 46,XX.

Karytype formulas continued.

An extra or missing chromosome is designated with a + or – symbol, respectively, before the number of the chromosome. Thus, the formula for a male with three chromosomes for chromosome 18 is 47, XY, +18 and the formula for a female with one chromosome 22 is 45, XX, -22.

Karyotype formulas continued.

The formula for a female with cri du chat syndrome is 46, XX, 5p-.

The formula for a male with a translocation (exchange of chromosome segments) between chromosomes 14 and 21 is 46, XY, t(14;21).

A translocation is any chromosomal aberration resulting from the interchange of parts between nonhomologous chromosomes.

Figure 8.24 Chromosomal translocations occurring between non-homologous chromosomes

The Philadelphia chromosome is a chromosome that results from a translocation between chromosome 9 and chromosome 22. The tip of chromosome 9 is translocated to chromosome 22. People with the Philadelphia chromosome have an increased risk of leukemia. When the translocation occurs, it produces a fusion protein that somehow causes the cell to become cancerous.

Figure 8.12 Frequency of Down syndrome related to a mother’s age.

Most children born with Down Syndrome is a result of non-disjunction during oogenesis resulting in an egg with an extra chromosome 21. However, in about 3% of children with Down Syndrome, it is a result of having one parent that has one of his/her chromosome 14’s fused with a chromosome 21 (A Robertsonian translocation).

Figure 8.27 Segregation of Robertsonian translocation between chromosome 14 and 21.

Dosage Compensation = Dosage compensation is the ability of an organism to compensate for the fact that a female inherits two X chromosomes and a male inherits an X and a Y chromosome.

In mammals, the mechanism of dosage compensation is achieved by X inactivation.

X-inactivation involves cells of an early mammalian female embryo randomly inactivating one of their two X chromosomes.

Inactivation of an X chromosome means that most of the genes from the inactivated X chromosome cannot be expressed.

In some cells of the early embryo, the paternally inherited X chromosome is inactivated and in other cells of the early embryo, the maternally inherited X chromosome is inactivated.

The X chromosome that is inactivated in a given cell of the early embryo is a random event.

Figure 8.7 Schematic diagram showing X-inactivation of cells of an early female embryo.

The inactivated X chromosome can be stained in some cell types and is called a Barr body. See figure 9.7.

Cells of an early embryo will inactivate all X chromosomes except one of them.
Therefore, a person that has three X chromosomes has cells with two inactivated X chromosomes and hence, two Barr bodies.

X-inactivation leads to a condition called mosaicism in females. Mosaicism occurs when different populations of a females cells express different forms of a gene. This is because a normal female is a mosaic for X-linked genes.

A females somatic cells contain genes that are expressed from only one of her two X chromosomes.
If a female contains an X-linked gene that contains two alleles A and B, some of her cells will express the A allele while other of her cells will express the B allele.

Mosaicism can be observed directly in women who are heterozygous for an X-linked recessive mutation that results in the absence of sweat glands. These women exhibit large patches of skin in which sweat glands are present (these patches are derived from embryonic cells in which the normal X chromosome remains active and the mutated X chromosome was inactivated) and other large patches of skin in which sweat glands are absent (these patches are derived from embryonic cells in which the normal X chromosome was inactivated and the mutant X chromosome remained active).

The condition described on the last slide is called anhidrotic ectodermal dysplasia.

The Calico Cat is a result of X-chromosome inactivation.

Two alleles affecting coat color are present in the X chromosomes in cats. One allele results in an orange coat color, the other in a black coat color.
A female that is heterozygous for coat color displays mosaicism and contains patches of orange and black coat color.

The tips of the X and Y chromosomes are called pseudoautosomal regions (PAR) regions.
PAR regions are homologous between the X and Y chromosomes.

The genes located at the PAR regions of an inactivated X chromosome can and are expressed.

The SRY gene is located near the PAR region but not within it on the short arm of the Y chromosome.

The SRY gene codes for a transcription factor that is involved in telling the developing embryo to develop into a male.

Figure 8.10 PAR regions of the X and Y chromosomes.

Crossing-over occurs between the X and Y chromosomes only at the PAR regions during prophase of meiosis I.

Read pages 307-309 for a detailed description of the origins of different groups of people based on genetic analysis of the Y chromosome.