The Best Human Genetic Disease
With the increasing ability to control infectious and nutritional diseases in developed countries there has come the realization that genetic diseases are a major cause of disability and death.
Families free of any known genetic disorder are indeed rare. Researchers have identified many thousands of different genetic disorders with distinct clinical symptoms. Of the 3 to 6 percent of newborns with a recognized congenital disorder, at least half involve a predominantly genetic contribution. The Best Human Genetic Disease
Genetic defects significantly contribute to pregnancy loss, with chromosomally abnormal fetuses accounting for nearly half of all spontaneous abortions (miscarriages). Genetic diseases cause about 30 percent of postnatal infant mortality in developed countries, and they are responsible for 30 percent of pediatric and 10 percent of adult hospital admissions. Finally medical investigators estimate that genetic defects-however minor are present in at least 10 percent of all adults. Thus,these are not rare events.
Classes of Genetic Disease
Researchers categorize most human genetic defects as resulting from chromosomal, single-gene Mendelian, single-gene non-Mendelian, or multifactorial causes.
The following sections briefly discuss each of these categories.
Diseases Caused by Chromosomal Aberrations
About 1 out of 150 live newborns has a detectable chromosomal abnormality. Yet even this high incidence represents only a small fraction of chromosome mutations since the vast majority are lethal and result in prenatal death or stillbirth.
Chromosomally abnormal fetuses are estimated to account for 50 percent of all first-trimester miscarriages and 20 percent of all second-trimester miscarriages. The Best Human Genetic Disease
Researchers group chromosome disorders into three principal categories:
Those that involve numerical abnormalities of the autosomes, those that involve structural abnormalities of the autosomes and those that involve the sex chromosomes. Autosomes are the 22 sets of chromosomes found in all normal human cells.
Scientists refer to chromosomes numerically according to a traditional sort order based on shape and other properties. Sex chromosomes make up 23rd pair of chromosomes in all normal human cells and come in two forms termed X and Y. In humans and many other animals it is the constitution of sex chromosomes that determines the sex the individual, such that XX results in a female and XY results in a male.
Numerical Abnormalities
Scientists generally believe that meiotic nondisjunction, the unequal division of chromosomes between daughter cells during either maternal or paternal gamete formation, causes numerical abnormalities involving either the autosomes or sex chromosomes.
Meiotic nondisjunction leads to eggs or sperm with additional or missing chromosomes. Although the biochemical basis of numerical chromosome abnormalities remains unknown, researchers have clearly identified the effect of maternal age, showing that older women face a significantly increased risk of conceiving and giving birth to a chromosomally abnormal child.
Structural Abnormalities
Structural abnormalities of the autosomes are even more common in the population than are numerical abnormalities and include translocations of large pieces of chromosomes as well as smaller deletions insertions or rearrangements. Indeed about 5 percent of all cases of Down syndrome result not from classic trisomy 21 but from the presence of excess chromosome 21 material attached to the end of another chromosome as the result of a translocation event.
If balanced structural chromosomal abnormalities may be compatible with a normal phenotype, although unbalanced chromosome structural abnormalities can be every bit as devastating as numerical abnormalities.
Because parents who are balanced carriers often inherit structural defects, couples who experience one pregnancy with a structural chromosomal abnormality face a significantly increased risk, compared to the general population, of encountering the same issue in future pregnancies. Clearly the likelihood of a recurrence would depend on whether a balanced form of the structural defect occurs in one of the parents.
Abnormalities of the Sex Chromosomes
About 1 in 400 male and 1 in 650 female live births demonstrate some form of sex chromosome abnormality although the symptoms of these conditions are generally much less severe than are those associated with autosomal abnormalities. Turner syndrome is a condition of females who in the classic form carry only a single X chromosome (45,X).
Turner syndrome involves a collection of symptoms, such as short stature, webbed neck, and incomplete or absent development of secondary sex characteristics, which lead to infertility. Researchers observe Turner syndrome in about 1 in 2,500 to 1 in 5,000 female live births. The 45,X karyotype accounts for 10 to 20 percent of the chromosomal abnormalities identified in spontaneously aborted fetuses.