THE HUMAN CHROMOSOME

WHAT IS KARYOTYPING? A typical karyotype is a

preparation of an individual’s metaphase chromosomes, sorted out by length, shape, centromere location, and other defining features. Large abnormalities in

chromosome structure or an altered chromosome number can be pinpointed by comparing an individual’s karyotype against a standard karyotype for the species.

MAKING A KARYOTYPE Human chromosomes are

in their most condensed form and easiest to identify when a cell is at metaphase in mitosis. Using blood cells

(typically) scientists induce metaphase, place the cells in a hypotonic solution (causing them to swell). The chromosomes move away from each other and then the cells are placed on a slide.

The cells are then photographed, and the photograph is cut with scissors or with a computers cut-n-paste tool.

The chromosomes are then lined up by size and shape.

SPECTRAL KARYOTYPES

A more recent diagnostic tool, uses a range of fluorescent dyes that bind to specific parts of chromosomes. Analysis of the

resulting rainbow-hued karyotype often reveals abnormalities that would not otherwise be discernable.

This chromosome (9) exchanged a segment of itself with the non-homologous chromosome 22.The end of chromosome 9 affects mitotic cell division and 22 affects expression of another gene.This mutation results in chronic myelogenous leukemia (CML) in which the body produces far too many white blood cells, which give rise to malignant cells in bone tissues.

AUTOSOMAL INHERITANCE PATTERNS Your body contains two types of

chromosomes: sex chromosomes and autosomal chromosomes. Sex chromosomes determine

whether you are male or female. Autosomes determine every

other trait in your body from the color of your eyes, to how fast your metabolism is.

Most human traits arise from complex gene interactions, but many can be traced to autosomal dominant or autosomal recessive alleles that are inherited in simple patterns. Some of these alleles cause

genetic disorders.

AUTOSOMAL DOMINANT INHERITANCE

To inherit an autosomal dominant mutation, you only need to inherit a single mutated or altered allele from either your mother or your father to show the trait. Polydactyly

This mutation causes an individual to grow more than 5 fingers or toes.

Only one parent needs to pass this onto their child for the child to have it.

One dominant allele (red) is fully expressed in carriers. Polydactyly, the inheritance of more than five fingers or toes, is an autosomal disorder.

AUTOSOMAL RECESSIVE INHERITANCE

To inherit an autosomal recessive mutation, you need to inherit mutated or altered alleles from BOTH your mother and your father to show the trait. Albinism

is characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin.

Both parents are heterozygous carriers of the recessive allele (red), and a child must inherit both recessive alleles to show the trait.

Tanzania has one of the highest incidences of albanism in the world! Over 150,000 albinos live there.

SEX DETERMINISM The Y chromosome carries

255 genes, one of which is the SRY gene that gives rise to the formation of testes.

The X chromosome carries 1,141 genes (no SRY gene). It includes genes that affect

the distribution of body hair and fat (which is why if your mother’s father isn’t bald, you won’t be either!)

Most of its genes deal with non-sexual traits like blood-clotting.

X-LINKED INHERITANCE Sometimes, genetic disorders

are carried on the X-chromosome. Recessive alleles on the X-

chromosome affect more males than females as the female has a second X that will mask the recessive X’s effects.

Males are not protected, because they only inherit one X chromosome.

An affected father cannot pass on the recessive allele to his son (because he’ll only pass on the Y-chromosome) but he WILL pass it onto his daughters.

EXAMPLES: Hemophilia A Red-Green Color Blindness Duchenne Muscular

Dystophy

Can you see the number? 12-20% of white males cannot! They have inherited red-green color blindness from their mothers, and have the inability to distinguish some or all shades of red and green.

ANEUPLOIDY In aneuploidy, cells usually

have one extra or one less chromosome. Autosomal aneuploidy is

usually fatal and linked to most miscarriages.

Aneuploidy typically arises through nondisjunction. Nondisjunction is where one or

more pairs of chromosomes do not separate as they should during meiosis or mitosis.

Polyloidy is where cells have three or more of each type of chromosome. Examples of Aneuploidy:

Down’s Syndrome Turner’s Syndrome Kleinfelter Syndrome XXX syndrome XYY condition

Down’s syndrome is caused by the presence of all or part of an extra 21 chromosome, known as trisomy 21. Down’s syndrome is associated with some impairment of cognitive ability and physical growth.

FEMALE SEX CHROMOSOME ABNOMALITIES

Sometimes females will inherit different amounts of X-chromosomes. (This is called aneuploidy or non-disjunction) Turner’s Syndrome

A female inherits one X chromosome and no corresponding X or Y chromosome.

98% of embryos spontaneously abort.

Results in several developmental abnormalities.

One characteristic sign of Turner’s Syndrome is the

presence of neck webbing and extra skin.

MALE SEX CHROMOSOME ABNORMALITIES Kleinfelter Syndrome

1 in 500 males inherit XXY chromosomes.

Results in normal range of intelligence, though may also have some learning disabilities.

Have several developmental side effects.

XYY condition 1 in 500 to 1,000 males

inherit XYY. Mild mental impariment.

A karyotype may be performed to determine the presence of either

Kleinfelter or XYY condition.

MAIN CATEGORIES

One or more changes in the physical structure of a chromosome may give rise to a genetic disorder or abnormality. Such changes are rare,

but they do occur spontaneously in nature. Some can also be

induced due to exposure to certain chemicals or irradiation.

DUPLICATION Even normal

chromosomes have DNA sequences that are repeated two or more times. Duplication can occur

through unequal crossovers at prophase I. Some duplications

cause neural problems and physical abnormalities.

Example: Huntington’s Disease

Normal chromosome

One segment repeated.

Three repeats

Huntington’s Disease causes progressive neurological degeneration. Symptoms typically do not appear until after age 30. It is cased by a repeating CAG sequence that disrupts normal brain cell development.

DELETION A deletion is a loss of

some portion of a chromosome, as by unequal crossovers, inversions, or chemical attacks. Most deletions cause

serious disorders or death. Missing or broken genes

disrupt the body’s growth, development, and metabolism.

Example: Cri-Du-Chat Syndrome

Segment C deleted

A tiny deletion from human chromosome 5 results in an abnormally shaped larynx and mental impairment. Crying infants sound like cats meowing. Hence, Cri-Du-Chat (cat-cry in French). Above is a picture of a male infant diagnose with Cri-Du-Chat, and the same boy 4 years later.

INVERSION With an inversion, part of the

sequence of DNA within the chromosome becomes oriented in the reverse direction, with no molecular loss. This can cause problems in

meiosis. Chromosomes can mispair,

and deletions may occur that can reduce viability of gametes. Some individuals

(carriers) do not even know that they have an inverted chromosome region until a genetic disorder or abnormality surfaces in one or more children.

segmentsG, H, Ibecomeinverted

Inversions and deletions often occur together, a result of unequal recombination events.

TRANSLOCATION With translocation, a

broken part of one chromosome becomes attached to another chromosome. Most translocations are

reciprocal, in that both of the two chromosomes exchange broken parts. Translocations often

cause reduced fertility, because affected chromosomes have difficulty segregating in meiosis. Example

Some sarcomas Lymphoma Myeloma Leukemia

reciprocal translocation

chromosome

nonhomologouschromosome