Genetic and environmental factors in disease development and cellular function

¶ … roles do genes play in determining cell structure and function? How is gene expression regulated?

Genes are composed of sequences of DNA which pass on the organism's genetic blueprint through the process of replication. "By serving as the blueprints of proteins in the body, genes ultimately influence all aspects of body structure and function... An error in one of these genes can lead to a recognizable genetic disease" (McCance & Huether 2012: 126).

What is the role of the environment in development of congenital disorders?

Genes have a considerable influence upon the probability of individuals developing particular disorders. For example, not every smoker develops lung cancer; not every overweight person develops type II diabetes. However, genes determine the likelihood that individuals will develop such disorders. The environment can trigger the expression of certain genes or support the conditions that make the manifestation of such conditions more or less likely to occur. In the case of lung cancer "most smokers do not develop lung cancer" but smoking can significantly increase the chances of developing the disorder, as can exposure to certain environmental toxins. "Some studies have suggested that mutations in a gene called FHIT may make some individuals more sensitive to the carcinogenic effects of tobacco smoke" (McCance & Huether 2012: 165). There is also a correlation between parent's blood pressure and the blood pressure of their children, yet scientists believe this is due to a combination of lifestyle factors, not genetics alone (McCance & Huether 2012: 165).

Q10. How might 1) over-expression of proto-oncogenes and 2) under-expression of tumor suppressor genes lead to abnormal cellular proliferation?

Proto-oncogenes regulate cell growth and differentiation, while tumor suppressor genes suppress the growth of tumors. If a proto-oncogene is damaged or has a chromosomal abnormality this could result in its transformation to an oncogene, or cancer cell. With under-expressed tumor suppressor genes, the likelihood of uncontrolled tumor growth is high.

Q13. Cri du chat syndrome

Cri du chat syndrome is caused by the deletion of genetic material on the p-arm of a chromosome. Affected infants make a "high-pitched cat-like cry" which gives the syndrome its name (Cri du chat syndrome, 2010, National Human Genome Research Institute). Other symptoms include "mental retardation, delayed development, distinctive facial features, small head size (microcephaly), widely-spaced eyes (hypertelorism), low birth weight and weak muscle tone (hypotonia) in infancy" (Cri du chat syndrome, 2010, National Human Genome Research Institute).

The reason for the chromosomal deletion is unknown. "The chromosomal deletion usually occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. People with cri du chat typically have no history of the condition in their family" (Cri du chat syndrome, 2010, National Human Genome Research Institute). However, in 10% of all cases, genetics may play a factor, when the developing fetus inherits a segment of chromosome with the deletion from an asymptomatic parent. "In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any medical problems; however, they can become unbalanced as they are passed to the next generation. A deletion in the short arm of chromosome 5 is an example of an unbalanced translocation, which is a chromosomal rearrangement with extra or missing genetic material" Cri du chat syndrome, 2010, National Human Genome Research Institute).

Learning verbal skills at a normal rate is a particular challenge for children with the syndrome. Only half of all individuals with the syndrome learn to communicate through speech. "Individuals learn to use short sentences, while others express themselves with a few basic words, gestures, or sign language (Cri du chat syndrome, 2010, National Human Genome Research Institute). Although some children have physical problems related to the disorder, including feeding difficulties, scoliosis and organ defects, the overall life expectancy of individuals with the syndrome is normal. The 'catlike' cry also tends to become less pronounced with age (Cri du chat syndrome, 2010, National Human Genome Research Institute).

Children with the syndrome require additional physical and academic support. Diagnosis is usually made based upon the 'cry' and can also be determined through chromosomal analysis. A recent study on of 91 patients from the Italian Registry fount that "half of the patients walk by themselves at three years old and that all learn to walk later; with regard to the language, 25% of the children are able to make short sentences at 4.5 years old, 50% at 5.5 and almost all the children make short sentences before the age of 10; 50% of the patients feed themselves with a spoon at 3.5 years old and dress at 5" (Mainardi 2006). Hyperactivity, "excessive attachment to objects" and self-injury were problems in approximately 50% of all patients in another study (Mainardi 2006).

Q14. Multifactorial inheritance

Twin studies are often used to examine the extent to which nature and nurture can contribute to the expression of diseases. On one hand, there is a clear link between genetics and the likelihood of developing certain conditions, such as schizophrenia. On the other hand, not every twin that develops a disease such as schizophrenia (or breast cancer, colon cancer, or diabetes) has a twin that develops the disorder. This indicates that environmental factors can also have an impact upon the expression of the disorder.

Because of the impact of the environment on gene expression, however, multifactorial inheritance can be very difficult to determine unless one uses twin studies, or individuals with the same genetic material. Multifactorial inheritance means that several, rather than simply one gene causes a particular trait to be expressed (such as height or intelligence). "As the number of multifactorial genes for the trait increases, the liability for the disease increases. When it reaches a threshold, the liability is so great that abnormality, what we call disease, results" (Multifactorial inheritance, 2012, Human Genetics).

There appears to be a different 'threshold of expression' for such multifactorial problems, including cleft palates, neural tube defects, or hip dysplasia. For example, "one of the environmental influences thought to contribute to hip dysplasia is the baby's response to the mothers' hormones during pregnancy. Once a child has been born with hip dysplasia, the chance for it to happen again in a male or female child is about 6% overall. In other words, there is a 94% chance that another child would not be born with hip dysplasia" (Multifactorial inheritance, 2012, Children's Hospital of Wisconsin). Studying twins with the same genetic composition helps researchers to better isolate which environmental factors predispose the expression of the genes.

Reference

Cri du chat syndrome. (2010). National Human Genome Research Institute. National Institutes of Health. U.S. Department of Health and Human Services

http://www.genome.gov/pfv.cfm?pageID=19517558

DNA replication. (2002). VBS homepage. Retrieved:

http://staff.jccc.net/pdecell/proteinsynthesis/dnarepli.html

Learning about Neurofibromatosis. (2010). National Human Genome Research Institute.

Retrieved:

http://www.genome.gov/14514225

Mainardi, Paola Cerruti. (2006). Cri du chat syndrome. Orphanet J. Rare Dis, 1(33).

Retrieved:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574300/

McCance, K.A. & Huether, S.E. (2010). Pathophysiology: The biologic basis for disease in adults and children (6th ed).

Multifactorial inheritance. (2012). Children's Hospital of Wisconsin. Retrieved:

http://www.chw.org/display/PPF/DocID/22923/router.asp

Multifactorial inheritance. (2012) Human Genetics. Retrieved:

http://www.uic.edu/classes/bms/bms655/lesson11.html