Chromosome , Karyotype and Numerical

Chromosomal Abnormalities

Dr.Aida Fadhel Biawi2013

Mutations range from single-base changes to entire extra sets of chromosomes. A mutation is considered a chromosomal aberration if it is large enough to see with a light microscope using stains and/or fluorescent probes to highlight missing, extra, or moved genetic material.

In general, excess genetic material has milder effectson health than a deficit. Still, most large-scale chromosomalabnormalities present in all cells disrupt or halt prenatal development.

As a result, only 0.65 percent of all newborns havechromosomal abnormalities that produce symptoms. An additional 0.20 percent have chromosomal rearrangements in which chromosome parts have been flipped or swapped, but they do not produce symptoms unless they disrupt genes that are crucial to health.

Cytogenetics is the subdiscipline within genetics that links chromosome variations to specific traits, including illnesses.

This chapter explores several chromosome–level abnormalitiesand their effects on health. Actual cases are used to describe some of them.

Required Parts of Chromosome : Telomeres and Centromeres

A chromosome consists primarily of DNA and proteins witha small amount of RNA, and is duplicated and transmitted—via mitosis or meiosis—to the next cell generation. Chromosomes have long been described and distinguished by size and shape, using stains and dyes to contrast dark heterochromatin with the lighter euchromatin (figure 13.1)

Heterochromatin consists mostly of highly repetitive DNA sequences, whereas euchromatin has more protein-encoding sequences.

A chromosome must include structures that enable it to replicate and remain intact—everything else is essentially informational cargo (protein-encoding genes and their controls).

The essential parts of a chromosome are:■ telomeres■ origin of replication sites, where replication forks begin to form■ the centromere

From figure 2.18 that telomeres are chromosome tips.

In humans, each telomere is many repeats of the sequence TTAGGG. In most cell types, telomeres shorten with each mitotic cell division.

The centromere is the largest constriction of a chromosomeand it is where spindle fibers attach when the cell divides.A chromosome without a centromere is no longer a chromosome. It vanishes from the cell as soon as division begins because there is no way to attach to the spindle.

Centromeres, like chromosomes, are made up mostlyof DNA and protein. Many of the hundreds of thousands ofDNA bases that form the centromere are repeats of a specific 171-base DNA sequence. The size and number of repeats are similar in many species, although the sequence differs. This suggests that these repeats have a structural role in maintaining chromosomes rather than an informational role.

Certain centromere- associated proteins are synthesized only when mitosis is imminent, forming a structure called a kinetochore that contacts the spindle fibers, enabling the cell to divide.

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Metaphase chromosome

Kinetochore

Kinetochoremicrotubules

Centromereregion ofchromosome

Sister Chromatids

- Centromeres are replicated toward the end of S phase.

Centromeres lie within vast stretches of heterochromatin.The arms of the chromosome extend outward from the centromere. Gradually, the DNA includes more protein-encoding sequences as distance from the centromere increases.

Karyotypes Chart Chromosomes

Even in this age of genomics, the standard chromosome chart, or karyotype, remains a major clinical tool. A karyotype displays chromosomes in pairs by size and by physical landmarks that appear during mitotic metaphase, when DNA coils tightly.

The 24 human chromosome types are numbered fromlargest to smallest—1 to 22. The other two chromosomes

are the X and the Y .

Early attempts to size-order chromosomes resulted in generalized groupings because many of the chromosomes are of similar size. Use of dyes and stains made it easier to distinguish chromosomes because they form patterns of bands.

Centromere position is one physical feature of chromosomes.A chromosome is metacentric if the centromeredivides it into two arms of approximately equal length. It is submetacentric if the centromere establishes one long arm and one short arm, and acrocentric if it pinches off only a smallamount of material toward one end ( figure 13.4 ). Some species have telocentric chromosomes that have only one arm, but humans do not. The long arm of a chromosome is designated q, and the short arm p ( p stands for “petite”).

Five human chromosomes (13, 14, 15, 21, and 22) have ends, called satellites, that extend from a thinner, stalklike bridge from the rest of the chromosome. The stalk regions do not bind stains well. The stalks carry many copies of genes encoding ribosomal RNA and ribosomal proteins. These areas coalesce to form the nucleolus, a structure in the nucleus where ribosomal building blocks are produced and assembled (see figure 2.3).

Figure 2.3

Benefits of Karyotypes

- Karyotypes are useful at several levels. When a baby isborn with the distinctive facial features of Down syndrome, akaryotype confirms the clinical diagnosis .

-Within families, karyotypes are used to identify relatives with a particular chromosomal aberration that can affect health. In one family, several adults died from a rare form of kidney cancer. Karyotypes revealed that the affected individuals all had an exchange, calleda translocation, between chromosomes 3 and 8. When karyotypes showed that two healthy young family members had the translocation, physicians examined and monitored their kidneys. Cancer was found very early and successfully treated.

- Karyotypes of individuals from different populationscan reveal the effects of environmental toxins, if abnormalities appear only in a group exposed to a particular contaminant.

Because chemicals and radiation that can cause cancer and birth defects often break chromosomes into fragments or rings,detecting this genetic damage can alert physicians to the possibility that certain cancers may appear in the population.

- Karyotypes compared among species can clarify evolutionary relationships. The more recent the divergence of two species from a common ancestor, the more closely related we presume they are, and the more alike their chromosome banding patterns should be. Our closest relative, according tokaryotypes, is the pygmy chimpanzee (bonobo). The human karyotype is also remarkably similar to that of the domestic cat, and somewhat less similar to those of mice, pigs, and cows.

Visualizing Chromosomes

Extra or missing chromosomes are detected by counting a number other than 46. Identifying chromosome rearrangements, such as an inverted sequence or an exchange of parts betweentwo chromosomes, requires a way to distinguish among the chromosomes. A combination of stains and DNA probes applied to chromosomes allows this. A DNA probe is a labeled piece of DNA that binds to its complementary base sequence on a particularchromosome.

Obtaining Cells for Chromosome Study

Any cell other than a mature red blood cell (which lacks a nucleus) can be used to examine chromosomes, but some cells are easier to obtain and culture than others. Skinlike cell collected from the inside of the cheek are the easiest to obtain for a chromosome test; white blood cells are used too. A person might require a chromosome test if he or she has a family history of a chromosomal abnormality or seeks medical help because of infertility.

Chromosome tests are commonly performed on cells from fetuses. Couples who receive a prenatal diagnosis of a chromosome abnormality can arrange for treatment of the newborn, if possible; learn more about the condition and contact support groups and plan care; or terminate the pregnancy.

These choices are best made after a genetic counselor or physician provides information on the medical condition and treatment options.

Chromosomes of a fetus are checked in several ways.Amniocentesis and chorionic villus sampling .

Chromosome Complements

The nucleus of every diploid cell, also called a SOMATIC CELL, contains the full complement of 46 chromosomes arranged in 23 pairs. One pair contains the sex chromosomes that establish gender, paired either as XX (female) or XY (male). The other 22 pairs are autosomes. The haploid cells, the gametes (spermatozoa and OVA), contain one half the chromosome complement. When gametes merge in CONCEPTION the diploid cell they form, the ZYGOTE, acquires the full chromosomal complement. The only cells in the body that do not have chromosomes are the erythrocytes, which do not have nuclei.

Autosomes carry the bulk of genetic code. Thousands of genes line each autosome, each in its ordained position. The sex chromosomes carry several hundred genes. The GENE positions, called loci (in the singular, each position is a locus), are constant. For example, the gene loci for the ABO BLOOD TYPE are always on chromosome 9, those for the rhesus (Rh) blood type are on chromosome 1, and those for EYE color on chromosomes 15 and 19.

The HUMAN GENOME PROJECT, completed in 2003, revealed the structure of chromosomes to be much larger and more complex than scientists previously had theorized. Chromosome 1, the largest CHROMOSOME, contains 2,968 genes. The smallest chromosome, the Y chromosome, contains 231 genes.

autosome - definition

                                

Autosome is a CHROMOSOME that appears as a pair in which both chromosomes are the same in either sex, also called a nonsex chromosome. In contrast, the sex chromosomes appear as a pair that is different in males and females. The human GENOME contains 22 autosomes and one pair of sex chromosomes for a total complement of 46 chromosomes as 23 pairs.

Sex Chromosome - definition

Sex Chromosome - the structure of GENETIC CODE that determines gender (male or female). The male sex CHROMOSOME has the appearance of the letter Y and the female sex chromosome has the appearance of the letter X. A combination of XY results in male and a combination of XX results in female. The Y chromosome contains fewer than 100 genes, while the X chromosome carries several hundred genes. A number of GENETIC DISORDERS are X-linked that is, they result from mutations that occur among genes the X chromosome carries. HEMOPHILIA and some forms of MUSCULAR DYSTROPHY (notably Duchenne’s and Becker’s) are X-linked genetic disorders.

Chromosomes in eukaryotes and prokaryotes are different

PROKARYOTESEUKARYOTESsingle chromosome plus plasmidsmany chromosomes

circular chromosomelinear chromosomes

made only of DNAmade of chromatin, a nucleoprotein (DNA coiled around histone proteins)

found in cytoplasmfound in a nucleus

copies its chromosome and divides immediately afterwards

copies chromosomes, then the cell grows, then goes through mitosis to organise chromosomes in two equal groups

OrganismChromosome numbers

Human46

Chimpanzee48

House Mouse40

Maize20

How to get Karyotype??

Final Step in Karyotype (Manual(

Karyotype (by software)

Metaphase chromosomes

Karyotyped chromosomes

Chromosome Groups

GroupChromosomesDescription

A1–3Largest; 1 and 3 are metacentric but 2 is submetacentric

B4,5Large; submetacentric with two arms very different in size

C6–12,XMedium size; submetacentric

D13–15Medium size; acrocentric with satellites

E16–18Small; 16 is metacentric but 17 and 18 are submetacentric

F19,20Small; metacentric

G21,22,YSmall; acrocentric, with satellites on 21 and 22 but not on the Y

Numerical chromosomal abnormalities

1- Polyploidy

The most drastic upset in chromosome number is an entireextra set. A cell with extra sets of chromosomes is polyploid.An individual whose cells have three copies of each chromosomeis a triploid (designated 3N, for three sets of chromosomes).Two-thirds of all triploids result from fertilization of anoocyte by two sperm. The other cases arise from formation of adiploid gamete, such as when a normal haploid sperm fertilizes a diploid oocyte. Triploids account for 17 percent of spontaneousabortions .

Very rarely, an infant survives as long as a few days, with defects in nearly all organs. However,certain human cells may be polyploid. The liver, for example, has some tetraploid (4N) and even octaploid (8N) cells.Polyploids are very common among flowering plants,including roses, cotton, barley, and wheat, and in some insects.

Polyploidy

2- Aneuploidy

Cells missing a single chromosome or having an extra one are aneuploid, which means “not good set.” Rarely, aneuploids can have more than one missing or extra chromosome, indicating defective meiosis in a parent. A normal chromosome number is euploid, which means “good set.”

Most autosomal aneuploids (with a missing or extra non-sex chromosome) are spontaneously abortedspontaneously aborted. Those that survive havespecific syndromes, with symptoms symptoms depending upon which chromosomesare missing or extra. Mental retardationMental retardation is common in aneuploidy because development of the brain is so complex andof such long duration that nearly any chromosome-scale disruptionaffects genes whose protein products affect the brain. Sexchromosome aneuploidy usually produces milder symptoms.

Most children born with the wrong number of chromosomes have an extra chromosome (a trisomy) rather than a missing one (a monosomy). Most monosomies are so severe that an affected embryo ceases developing. Trisomies and monosomies are named for the chromosomes involved.

The meiotic error that causes aneuploidy is called nondisjunction.Recall that in normal meiosis, homologs separateand each of the resulting gametes receives only one member ofeach chromosome pair. In nondisjunction, a chromosome pairfails to separate at anaphase of either the first or second meioticdivision. This produces a sperm or oocyte that has two copies ofa particular chromosome, or none, rather than the normal onecopy ( figure 13.12 ). When such a gamete fuses with its partnerat fertilization, the zygote has either 45 or 47 chromosomes,instead of the normal 46. Different trisomies tend to be causedby nondisjunction in the male or female, at meiosis I or II.

3- Mosaicism : denotes the presence of two or more populations of cells with different genotypes OR DIFFERENT CELL LINES in one individual who has developed from a single fertilized egg .

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