The Structure and Function of Human Chromosomes - Coursework Example

Introduction The DNA, which carries genetic information in biological cells, is normally packed in the form of one or more large macromolecules called chromosomes. A chromosome can be defined as the visible state of genetic material during a phase of the division of the cell (metaphase). Humans have 23 pairs of chromosomes, which make the diploid number 46. (Molecular Biology Notebook, 2004.) Structure and function A chromosome contains many genes, regulatory elements and other intervening nucleotide sequences in a very long, continuous piece of DNA. In eukaryotes, the uncondensed DNA is present inside the nucleus, wrapped around structural proteins called histones. Together, this composite material is called chromatin. There are two types of chromatin: euchromatin, which consists of active DNA (Wikipedia, 2005) and heterochromatin, which consists of mostly inactive DNA but it controls the metabolism of the chromosome, biosynthesis of the nucleic acids and the energy metabolism (Verma PS, Agarwal VK, 1988.) Before cell division by mitosis, each chromosome is duplicated (during the S phase of the cell cycle). As mitosis begins, the duplicated chromosomes condense into short (~ 5 µm) structures. These duplicated chromosomes are called dyads. The dyads are held together at their centromeres. In humans, these centromeres contain 1 million base pairs of DNA. While they are still attached, the duplicated chromosomes are called sister chromatids. At each centromere, a complex of proteins forms. This is called kinetochore, and it serves as the attachment point for the spindle fibres that will separate the sister chromatids, as mitosis proceeds into anaphase. From the centromere, two arms extend. The shorter of the two arms is called the p arm, and the longer is the q arm. A series of alternating light and dark bands called G bands are revealed when stained with the trypsin-giemsa method. These G bands are numbered and provide "addresses" for the assignment of gene loci (Chromosomes, 2004.) Chromosomes come in pairs, called homologous pairs. Humans have 23 pairs of chromosomes. Homologous chromosomes are a result of sexual reproduction, and the homologous pairs are the maternal (inherited from the mother) and paternal (inherited from the father) versions of the same chromosome, so they have the same sequence of genes. One pair of chromosomes is different in males and females, called the sex chromosomes, and are non-homologous in one of the sexes. In humans, the sex chromosomes are homologous in females (XX) and non-homologous in males (XY). ( Verma PS, Agarwal VK 1988.) DNA Structure James Watson and Francis Crick described the structure of DNA in 1953. According to them, the DNA molecule consists of two polynucleotide chains wrapped helically around each other, with the sugar-phosphate chain on the outside and the purines and pyrimidines on the inside of the helix. Adenine and guanine are purines, while cytosine and thymine are pyrimidines. The two polynucleotide strands are held together by hydrogen bonds between specific pairs of purines and pyrimidines (adenine with thymine and guanine with cytosine) The two DNA strands form a helical spiral, winding around a helix axis in a right-handed spiral The two polynucleotide chains run in opposite directions. Both polynucleotide strands remain separated by 20 Ao distance (Verma PS, Agarwal VK 1988.) Cytogenetical functions of chromosomes The chromosomes are the most significant components of a cell, controlling most of the biological and genetic activities of a cell. They contain the genetic material, the DNA. The DNA is responsible for the genetic propagation of most inherited traits. During reproduction, DNA is replicated and transmitted to the offspring. (Verma PS, Agarwal VK 1988.) Down’s syndrome Down syndrome or Trisomy 21 is the most common chromosomal abnormality. There are three genetic mechanisms: 1. The most common type is called non-disjunction, where there is an entire extra chromosome 21 in all cells. 2. Mosaic, where Trisomy 21 cells are mixed with a second cell line, usually "normal" (46, XX or 46, XY.) 3. Translocation, where part or all of chromosome 21 is translocated to another chromosome; usually number 14, 21, or 22 (Bettencourt J, 1998.) Only five percent of Down syndrome cases may be hereditary. Nondisjunction occurs in 95 percent, mosaicism occurs in 2 percent, Robertsonian translocation occurs in the remaining 3 percent. Most chromosome-21 translocations are sporadic. (Bettencourt J, 1998). However, some are inherited from a parent who carries the translocation balanced by a chromosome deletion. (Newberger DS, 2000) Diagnosis and treatment Prenatal screening (Kumar S, OBrien A, 2004)  11-14 weeks Nuchal translucency (NT) by ultrasound. Combined test (NT, hCG, and PAPP-A) 14-20 weeks Triple test (hCG, AFP, and uE3) Quadruple test (hCG, AFP, uE3, and inhibin A) 11-14 weeks and 14-20 weeks Integrated test (NT, PAPP-A, inhibin A, hCG, AFP, and uE3) Serum integrated tests (PAPP-A, inhibin A, hCG, AFP, and uE3) Amniocentesis: It is one of the commonest methods, done for detecting "high-risk" pregnancies at 16 weeks, selected on the basis of maternal age being greater than 35 years or a previously affected pregnancy. Since most babies with Down syndrome are born to mothers less than 30 years old, this test, despite being extremely sensitive, misses the majority of Trisomy 21 pregnancies because of the restriction of its use to the older age group. (Trumble S, 1993) Chorionic Villus Sampling: In this procedure, a transvaginal biopsy of the developing placenta is done at 10 to 12 weeks of gestation. Although this test has the advantage of earlier detection of chromosomal abnormalities, it is associated with a higher rate of post-procedure miscarriage. (Trumble S, 1993) Unfortunately, there is no specific treatment for Down syndrome. Treatment is mainly aimed at specific health problems. Special education and training is offered for mentally handicapped children. Genetic counselling and karyotyping of parents helps in prevention in further offspring’s. The important medical problems, according to the age group, can be summarized as follows: Neonatal period: Endocardial cushion defects, septal defects, Fallots tetralogy, duodenal atresia, pyloric stenosis, Hirschsprungs disease, tracheo-oesophageal fistulae, congenital cataracts, glaucoma, hypotonia, congenital hypothyroidism, congenital dislocation of the hips. Childhood and adolescence: Physical milestones and socialisation may be delayed, difficult speech, significant hearing impairments, refractive errors or strabismus, cataract, atlantoaxial instability, small, irregularly spaced and misshapen teeth, and slightly delayed menarche in girls. Adulthood: Hypothyroidism, psychiatric disorders, dementia. ************************************************************************** References Bettencourt J (1998). Down Syndrome: Trisomy 21. Biology Alive! Retrieved November 16, 2005 from, http://www.altonweb.com/cs/downsyndrome/index.htm?page=bettencourt.html Chromosomes (2004). Retrieved November 16, 2005 from, http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Chromosomes.html#Structure Kumar S, OBrien A (2004). BMJ 2004; 328:1002-1006 Molecular Biology Notebook (2004). Retrieved November 16, 2005 from, http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/chromo.htm Newberger DS (2000). Down Syndrome: Prenatal Risk Assessment and Diagnosis. American Family Physician. Retrieved November 16, 2005 from, http://www.aafp.org/afp/20000815/825.html Trumble S, 1993. How to Treat People with Down Syndrome. Retrieved November 16, 2005 from, http://www.nas.com/downsyn/trumble.html Verma PS, Agarwal VK 1988. Cell Biology, Molecular Biology and Genetics, sixth edition, pp. 407-408 Wikipedia, the free encyclopedia, 2005. Chromosome. Retrieved November 16, 2005 from, http://en.wikipedia.org/wiki/Chromosome Read More