Down Syndrome

Down syndrome, also known as Trisomy 21, is a genetic disorder that results from an individual having an extra copy of chromosome 21. Human cells have 46 chromosomes which are arranged in 23 pairs. A person inherits 23 pairs of chromosomes from the mother and 23 pairs from the father. In Down syndrome, an individual inherits two chromosomes 21 from one parent instead of one, and one chromosome 21 from the other parent, leading to three copies of chromosome 21 instead of two copies. Down syndrome is caused by nondisfunction where a pair of chromosome number 21 fails to detach during formation an egg. When this egg unites with a normal sperm to form a zygote, the zygote ends up having three copies of chromosomes 21 instead of two.

Individuals with Down syndrome have distinct facial abnormality features such as a small broad nose, flat face, large tongue, abnormally shaped ears and slanting eyes. They are also at a high risk of developing numerous medially significant problems like leukemia, gastrointestinal tract obstruction, hart defects, respiratory infections, hypothyroidism and hearing loss. They also display moderate to severe physical and mental retardation, and usually grow and develop more slowly than their peers.

Mendel's law of segregation

The Mendel's, the law of independent assortment and the law of segregation form the foundation of genetics. These two laws describe basic and important rules on how traits are passed from parents to offspring and how human traits such as Down syndrome are inherited following patterns that conform to Mendel's law.  Mendel's law of segregation states that when a person produces gametes, the copies of the gene separate and each gamete obtains one copy only. The two members of the pair of alleles segregate or separate into two diverse gametes and exert their impact in an offspring as one of a novel pair of alleles.  Segregation occurs as a result of separate carriage of genes on the chromosomes, which are not blended or altered through forming pairs (Pierce, 2005).

Chromosome segregation is the coordinated movement of chromosomes to the opposite poles of cell during cellular reproduction or mitosis of during production of sex cells or meiosis. Chromosomes separate along a spindle fiber that joins at a site known as the kinetochore to chromosome centromere during the anaphase stage of mitosis. In order to make sure that equal segregation takes place, sister chromatids are connected from the period they are synthesized to the period they are segregated.

Failure of chromosomes to segregate implies that there would be no a means through which genetic information can be passed from a single cell to the next. However, this procedure is not flawless and chromosome abnormalities may occur when chromosomes fail to segregate properly. The alterations may be of numerical of structural nature. Numerical alterations lead to addition, or aneuploidy, or individual chromosomes being lost from the usual set of 46. If anomaly entails addition of an entire set of chromosomes, it is referred to as polyploidy. Structural aberrations involve rearrangement of genetic material between or within chromosomes.

Korenberg (2004) argues that rearrangements of this form may be balanced, implying that there isn't a loss of genetic material, or unbalanced, implying that there is a loss or gain of a portion of the chromosome. Numerical abnormalities usually emerge as a result of failure of the chromosomes to properly segregate, a phenomenon referred to as disjunction. Nondisjunction during first division of meiosis emerges from the failure of the homologous chromosomes to separate out to opposite poles of cell. Nondisjunction may also take place at meiosis two when sister chromatids fail to segregate.  

Nondisjunction during meiosis 1 and during meiosis two both leads to generation of gametes that are disomic, implying that there is an additional chromosome, or nullisomic, implying that a chromosome is lost.  During fertilization, when a nullisomic gamete unites with a gamete that has normal number of chromosomes, it gives rise to a zygote that has monosomy, or one chromosome less than normal. When a disomic gamete unites with a gamete that has normal number of chromosomes gives rise to a zygote that has trisomy, implying that the zygote has an additional chromosome, and this is the case in Down syndrome.

Mendel's law of independent assortment

The Mendel's law of independent assortment, also known as law of inheritance, states that all alleles of diverse genes sort out independently of each other during gamete formation. Independent assortment occurs during meiosis one in eukaryotic cells, particularly metaphase one, to generate a gamete with a blend of the organism's paternal and maternal chromosomes. Human somatic cells usually contain 23 pairs of chromosomes, with 22 pairs being autosomes and one pair being sex chromosomes XY in males and XX in females.  

Human cells divide through two ways. The initial usual cell division is called mitosis, through which the body grows and develops. During mitosis, once cell divides into two cell having the same type and number of chromosomes as parent cell. However, meiotic cell division takes place in testicles and ovaries and comprises of one cell dividing into two, with resulting cells possessing half the number of chromosomes of parent cell. Therefore, normal sperm and egg cells have only 23 chromosomes instead of 46 chromosomes as somatic cells (Mays, 2006).

Chromosomes are inherited as a cluster implying that at the time of cell division, they function as a unit other than independently. The presence of linkage groups attributes to the reason why some traits like Down syndrome do not abide by the Mendel's law of independent assortment of recombination of the genes and the traits that these genes control. Errors taking place during mitosis or meiosis can result to chromosomal aberrations where large portions of chromosomes or whole chromosomes are added or missing.

If the gamete possessing a chromosomal aberration takes part in fertilization, the zygote that is formed which contain an abnormal number of chromosomes and DNA content as in the case of Down syndrome where an individual has 47 chromosomes instead of 46 as a result of one extra chromosome in the 21 or Trisomy of chromosome 21. Chromosomes hold genes which direct production of a wide range of materials that the body requires. In Down syndrome, the existence of an additional set of genes results to overexpression of the genes involved, resulting to increased production of particular materials.

Nondisjunction and Down syndrome

Down syndrome or Trisomy 21 occurs as a result of a meiotic nondisjunction event. A normal gamete either a sperm or egg contains one copy of each chromosome. When united with a gamete from the other parent during fertilization and conception, the resulting offspring has 46 chromosomes. Chromosomes in cells are made up of proteins and genetic information in form of DNA.

During meiosis, chromosomes are required to divide and go to diverse regions of the cell, a meiotic step known as disjunction. However during cell division, a chromosome fails to detach and stays connected with its pair chromosome. This leads to one of the newly formed cells possessing 24 chromosomes and the other possessing 22 chromosomes, an error called nondisjunction (Antonarakis, 2004).

When cells with nondisjunction error unite with a typical cell, the fertilized egg ends up having uneven number of chromosomes. Therefore, in the case of Down syndrome of a gamete is produced with an additional copy of chromosome 21 and when united with a typical gamete from the other parent, the zygote has 47 chromosomes, with three copies of chromosome number 21. Trisomy 21 causes approximately 95 percent of Down syndrome, with 88 percent coming from meiotic nondisjunction in maternal gamete and 8 percent from nondisjunction in paternal gamete.

Chromosomal translocation and Down syndrome

Down syndrome may also be caused by a chromosome translocation, which is a chromosome anomaly caused by rearrangement of portions between non-homologous chromosomes deviation in the composition of genes within a chromosome takes place when a chromosome breaks, and the broken parts connect with partner chromosome if the breakage has occurred in similar locations (Hattori, 2000).

The exchange of genes amid chromosomes, usually referred to as crossing over, normally occurs during meiosis, when the total chromosome number is halved.  In Translocation Down Syndrome, the additional material in chromosome 21 occurs as result of Robertsonian translocation which usually entails exchange of genetic material between nonhomologous chromosomes.

The long arm of chromosome number 21 is connected to another chromosome, usually chromosome 14 or itself.  The long arms of these two acrocentric chromosomes are translocated to generate a sole long chromosome, leaving out the short arm which fails to separate out, therefore lessening the entire chromosome number.  Translocation Down syndrome might be de novo, implying that they are not inherited but occurring at the period when an individual is being conceived. It also might be inherited from a parent who has balanced translocation. The person possesses two copies of everything on chromosome number 14, and two copies of all material on long arm of chromosome 21( Costa,  & Patterson, 2005 ).

The person has a single copy of the material on short arm of chromosome 21, but it does not have an apparent effect. People with this type of chromosomal arrangement are phenotypically normal. At meiosis, chromosomal arrangement meddles with normal separation of the chromosomes and the resulting possible arrangements are normal 21 and normal 14,  Translocated 14/21 only, Translocated 14/21 and normal 21, and Normal 14 only.  When the normal 14 only is united with a normal gamete from the other parent it becomes lethal and leads to spontaneous abortion.  When the Normal 14 and normal 21 is united with a typical gamete from the other parent, it results to a normal offspring, while a translocated 14/21 results to an offspring with translocation Down syndrome.

Mosaic Down Syndrome occurs when some body cells are normal and other cells possess trisomy 21, an arrangement known as mosaic. This may take place as a result of a nondisjunction occurrence during early stages of cell division resulting to a portion of the cells with trisomy21. It may also occur when an embryo with Down syndrome experiences nondisjunction and some of cells within the embryo regress back to normal chromosomal arrangement.

Conclusion

Down syndrome is a genetic disorder that occurs as a result of an additional chromosome. Down syndrome is caused by occurrence of an additional chromosome 21 which makes the person to have three copies of chromosome 21 instead of two. The person also has 47 chromosomes in the cells instead of the normal 46 which leads to physical and mental retardation with abnormal physical characteristics such as large tongue, flat face and slanting eyes.

Down syndrome as a human trait is inherited following patterns that conform to Mendel's law of segregation and independent assortment. Instead of chromosome 21 separating and moving to opposite regions of the cell during meiosis, they fail to detach resulting to disjunction which makes the reproductive cell to have abnormal number of chromosomes. In Down syndrome, the egg gains an additional copy of chromosome 21, and when it unites with a normal sperm, the resulting child has three copies of chromosome 21.