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 Genetics Information:
 รายละเอียดเรื่องราวของระบบ
 พันธุกรรม

  Introduction
  Background Information
  Genetic Disorders
   
- autosomal dominant, 
   
- autosomal recessive, 
   
- X-linked dominant, 
    - X-linked recessive.

  Examples of single
     gene disorders 

  Chromosome Disorders
  Multifactorial Disorders 
  Mitochondria Disorders

 
Autosomal dominant 
    
Information:

 
Sex-linked dominant 
     Information:

 
Sex-linked recessive    
     Information:
 
Autosomal recessive 
     Information
:

 
Chromosome 
     Information:
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Gene Information:
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 Genetics Information:      

Genetics Information:
INTRODUCTION
It is common knowledge that a person's appearance (e.g., height, hair color, skin color, eye color, etc) are determined by genes. A person's mental abilities and natural talents are certainly affected by heredity. Some diseases (or susceptibility to acquire a disease) are also known to be genetically related.

An inherited abnormal trait or anomaly may be of no real consequence to a person's health or well being (for example, a white splotch of hair or an extended ear lobe). An inherited anomaly may be of minor consequence (for example, color blindness). On the other hand, an inherited disorder may also have multiple effects resulting in dramatically decreased quality or length of life. For some genetic disoders, genetic counseling and prenatal diagnosis may be advised.

The terms anomaly, abnormality, disorder, defect, disease, and syndrome are not used consistently and do not have precise definitions.


BACKGROUND INFORMATION
Human beings have cells with 46 chromosomes (2 sex chromosomes and 22 pairs of autosomal, that is, non-sex chromosomes). Males are 44,XY; females are 44,XX. Each chromosome is comprised of 2 extremely long DNA molecules in combination with chromosomal proteins. Genes are defined by intervals along one of the DNA molecules. The location of the gene is called the locus. Most genes carry information which is necessary to synthesize a protein. The pairs of autosomal chromosomes (one from mom and one from dad) carry basically the same information; that is, each has the same genes, but there may be slight variations in the DNA sequence of nucleotide bases in each gene. Alleles are different variants of a particular gene.

The information contained in the nucleotide sequence of a gene is transcribed to mRNA (messenger RNA) by enzymes in the cell's nucleus and then translated to a protein in the cytoplasm. This protein may be a structural constituent of a given tissue. It may be an enzyme which catalyzes a chemical reaction, or it may be a hormone. There are also many other potential functions for proteins.

If a gene is abnormal, it may code for an abnormal protein or for an insufficient amount of a normal protein. Since the autosomal chromosomes are paired, there are 2 copies of each gene. If one of these genes is defective, the other may code for sufficient protein so that the abnormality is not clinically apparent. This is called a recessive disease gene. If one abnormal gene somehow produces disease, this is called a dominant hereditary disorder. In the case of a dominant disorder, if one abnormal gene is inherited from mom or dad, the child will show the disease. In the case of a recessive disease, if one abnormal gene is inherited, the child will not show clinical disease, but they will pass the abnormal gene to 50% (on average) of their offspring.

A person with one abnormal gene is termed HETEROZYGOUS for that gene. If a child receives an abnormal recessive disease gene from both parents, the child will show the disease and will be HOMOZYGOUS for that gene. If two parents are each heterozygous for a particular recessive disease gene, then 25% of their children (on average) will be homozygous for that gene and show the disease. If one parent is homozygous and the other heterozygous, then 50% of the children will be homozygous.


GENETIC DISORDERS:
Almost all diseases have a genetic component, but the importance of that component varies. Disorders where genetics play an important role, so-called genetic diseases, can be classified as single gene defects, chromosomal disorders, or multifactorial. Single-gene defects are also called mendelian disorders.

A single gene disorder is one that is determined by a specific allele at a single locus on one or both members of a chromosome pair. Single gene defects are rare, with a frequency of less than 1 in 500 births, but since there are about 3000 known their combined impact is significant. The incidence of serious single gene disorders is estimated to be about 1 in 300 births.

Single-gene disorders are characterized by the pattern of transmission in families; this is called a pedigree. A kindred includes the relatives outside of the immediate family. The affected individual that initially comes to light or is of immediate interest is called the proband. The brothers and sisters of the proband are called sibs.

There are only four basic patterns of single gene inheritance: 
  autosomal dominant, 
  autosomal recessive, 
  X-linked dominant, and 
  X-linked recessive.


The observed effect of an abnormal gene (the appearance of a disorder) is called the abnormal phenotype. A phenotype expressed in the same way (in both homozygotes and heterozygotes) is dominant. A phenotype expressed only in homozygotes (or, for X-linked traits expressed in males but not females) is recessive. Heterozygotes for a recessive gene are called carriers. They usually don't express the phenotype clinically, but it can frequently be identified by sensitive laboratory methods.

In autosomal dominant inheritance, the abnormality or abnormalities appear in every generation. Every affected child has an affected parent and, on average, each child of an affected parent has a 50% chance of showing the disease. Normal members of the family do not transmit the disease. Males and females are equally likely to have the disease and to transmit the disease. Male-to-male transmission can occur (unlike with X-linked dominant inheritance) and males can have unaffected daughters (unlike with X-linked dominant inheritance).

In autosomal recessive inheritance, the parents of an affected individual may not express the disease. On average, the chance of an affected child's brothers or sisters having the disease are 1 in 4. Males and females are equally likely to be affected. For a child to have symptoms of an autosomal recessive disorder, the child must receive the recessive gene from BOTH parents. Because these disorders are rare, when a child has symptoms of an autosomal disorder there is a chance that the parents are related.

In X-linked recessive inheritance, the incidence of the disease is much higher in males than females. Since the abnormal gene is carried on the X chromosome, males do not transmit it to their sons; they do transmit it to all their daughters. The presence of one normal X chromosome masks the effects of the X chromosome with the abnormal gene so almost all of the daughters of an affected man appear normal, but they are all carriers of the abnormal gene. The sons of these daughters then have a 50% chance of receiving the defective gene.

In X-linked dominant inheritance, the presence of the defective gene makes itself manifest in females even if there is also a normal X chromosome present. Since males pass the Y chromosome to their sons, affected males will not have affected sons, but all of their daughters will be affected. Sons or daughters of affected females will have a 50% chance of getting the disease (except for the rare case of the female with two abnormal genes).


EXAMPLES OF SINGLE GENE DISORDERS:
Autosomal recessive:
Cystic fibrosis (CF) is a very common hereditary disorder (1 out of 2000 caucasian births). The normal function of the protein is to transport chloride ions into certain cells. Deficiency of this protein somehow results in the accumulation of thick mucus in the lungs and other parts of the body. This situation compromises respiration and greatly increases the chance of pulmonary infections. Affected individuals rarely survive to the age of 30.
Phenylketonuria (PKU) is a common genetic disorder (1 out of 12,000 births) which results from a deficient enzyme required for the metabolism of the amino acid phenylalanine. Failure to recognize the disorder early in life results in mental retardation. Many states require all newborns to be screened for this disease.
AAT deficiency is a disorder seen in about 1 out of 10,000 births. The normal function of the protein is to inhibit enzymes which escape from white blood cells in the process of destroying invading bacteria. Affected individuals are much more likely to develop emphysema than usual.
Sickle cell anemia is a disorder common in individuals with an African ethnic background. The high frequency of the gene probably relates to the fact the the heterozygotes are resistant to malaria. The homozygotes have a predominance of an abnormal hemoglobin in their red blood cells. This abnormal protein causes the red blood cells to assume abnormal shapes and to lyse in small blood vessels under conditions of reduced oxygen pressure.
ADA deficiency is a rare immunodeficiency disorders, sometimes called the "boy in a bubble" disease, which results from the deficiency of an enzyme called adenosine deaminase. This enzyme is important for the normal function of lymphocytes which are the primary components of the immune system. This disease has the distinction of being the first to be treated effectively by genetic engineering, where some of the patients lymphocytes are removed from the body, injected with a normal gene, then reintroduced to the body.

X-linked recessive:
Duchenne muscular dystrophy is a very common (1 out of 3500 male births) disorder which results from the presence of an abnormal muscle protein. Muscles of young boys gradually deteriorate until even the muscles required for normal respiration become ineffective. These boys usually die of pulmonary infections before the age of 20.
Hemophilia A is seen in 1 out of 10,000 male births. The defective protein (coagulation factor VIII) is require for normal blood clotting. Affected individuals require injections of the protein or transfusion of blood products to prevent internal bleeding. Until recently when the genetically engineered protein became available, many of these individuals contracted hepatitis or AIDS as a result of their many transfusions.
Tay-Sachs disease is a disorder which is seen almost solely in Ashkenazi Jew populations. The incidence in this population has been substantially reduced (from about 1 out of 900) as a result of massive screening programs. The affected protein is an enzyme necessary to breakdown lipids in the membranes of cells. Abnormal membrane fragments accumulate and cause a deterioration of the nervous system. Affected individuals die before the age of 3.

Autosomal dominant:
Familial hypercholesterolemia (FHC) is a fairly common disorder (1 out of 500 individuals are heterozygous). The affected gene codes for a protein which is found on the external surface of most of the body's cells. This so-called receptor protein mediates the uptake of cholesterol into the cells. This cholesterol is transported in the blood by a lipoprotein called LDL. When LDL can't get into cells it increases to high levels in the blood. High levels of LDL (with it's associated cholesterol) increases the risk of developing arteriosclerosis and coronary artery disease. Homozygous individuals (about 1 out of 1,000,000 births) have extremely high levels of LDL and develop coronary heart disease in childhood.
Huntingtons disease is a neurodegenerative disease which doesn't appear until approximately age 30. It has recently become possible to test for the presence of the abnormal gene at any age. This information may be of great interest to individuals who know they will develop the disease later in life since they may wish to modify their plans in regards to marriage, childbearing, etc.

X-linked dominant:
Only a few, very rare, disorders are classified as X-linked dominants. One of these is hypophosphatemic rickets (also called vitamin D resistant rickets). In this case a protein in the kidneys is defective. This protein normally transports phosphate from the urinary filtrate back into the blood. Since the amount of phosphate in the blood is much lower than normal, the bones are chronically stimulated to release calcium and phosphate by hormones such as parathormone. This results in fragile and abnormally structured bones.


CHROMOSOMAL DISORDERS
In chromosomal disorders, the defect is due not to a single gene, but to an excess or deficiency of the genes contained in a whole chromosome or chromosome segment.

Downs syndrome is the most common chromosomal disorder (1 out of 800). Affected individuals have an extra copy of chromosome 21. This unbalanced set of genes results in moderate to severe mental retardation and numerous physical changes. 
Klinefelters syndrome (1 out of 1000 males) and
Turners syndrome (1 out of 5000 females).


MULTIFACTORIAL DISORDERS
Many of the most common diseases which affect humans undoubtedly involve interactions of numerous genes, e.g., coronary heart disease, hypertension, stroke, and various kinds of cancer. These are currently active areas of research.


MITOCHONDRIAL DISORDERS
Mitochondria are small organelles present in most of the body's cells which function in the conversion of certain chemicals in our food, in the presence of oxygen, to the common currency of energy inside cells, i.e., ATP. Mitochondria contain their own private DNA. In recent years several hereditary disorders have been shown to result from mutations in mitochondrial DNA.



12. Autosomal dominant 
Autosomal dominant 
Information:

Definition:
A single abnormal gene on one of the autosomal chromosomes (one of the first 22 "non-sex" chromosomes) from either parent can cause the disease. One of the parents will have the disease (since it is dominant) in this mode of inheritance and that person is called the CARRIER. Only one parent must be a carrier in order for the child to inherit the disease.

BACKGROUND:
The inheritance of genetic diseases, abnormalities, or traits is described by both the type of chromosome the abnormal gene resides on (autosomal or sex chromosome) and by whether the gene itself is dominant or recessive.

Autosomally inherited diseases are inherited through the non-sex chromosomes, pairs 1 through 22. Sex-linked diseases are inherited through one of the "sex chromosomes", the X chromosome (diseases are not inherited through the Y chromosome).

Dominant inheritance occurs when an abnormal gene from ONE parent is capable of causing disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair.

Recessive inheritance occurs when BOTH matching genes must be abnormal to produce disease. If only one gene in the pair is abnormal the disease is not manifest or is only mildly manifest; however the disease can be passed on to the children.

STATISTICAL CHANCES OF INHERITING A TRAIT:
For an autosomal dominant disorder: If one parent is a carrier and the other normal there is a 50% chance a child will inherit the trait.

In other words, if it is assumed that 4 children are produced, one parent is carrier and exhibits disease, the STATISTICAL expectation is for:

2 children normal
2 children with the disease
This does not mean that children WILL necessarily be affected; it does mean that EACH child has a 50:50 chance of inheriting the disorder.

RELATED TOPICS:
autosomal recessive
genetic counseling and prenatal diagnosis
sex-linked dominant
sex-linked recessive

For detailed information, see heredity and disease (genetics).




13. SEX-LINKED DOMINANT 
SEX-LINKED DOMINANT 
Information:

Definition:
A single abnormal gene on the X chromosome can cause the disease. This disease is transmitted equally to boys and girls. This is a rare mode of transmission.

BACKGROUND:
The inheritance of genetic diseases, abnormalities, or traits is described by both the type of chromosome the abnormal gene resides on (autosomal or sex chromosome) and by whether the gene itself is dominant or recessive.

Autosomally inherited diseases are inherited through the non-sex chromosomes, pairs 1 through 22. Sex-linked diseases are inherited through one of the "sex chromosomes", the X chromosome (diseases are not inherited through the Y chromosome).

Dominant inheritance occurs when an abnormal gene from ONE parent is capable of causing disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair.

Recessive inheritance occurs when BOTH matching genes must be abnormal to produce disease. If only one gene in the pair is abnormal the disease is not manifest or is only mildly manifest; however the disease can be passed on to the children.

STATISTICAL CHANCES OF INHERITING A TRAIT:
For an X-linked dominant disorder: If the father carries the abnormal X gene all of his daughters will have the disease and none of the sons will have the disease. If the mother carries the abnormal X gene half of all their children (daughters and sons) will have the disease.

In other words, if it is assumed that 4 children are produced (2 male and 2 female), the mother is a carrier (1 abnormal X, she has disease), and the father is normal, the STATISTICAL expectation is for:

2 children (1 girl & 1 boy) with disease
2 children (1 girl & 1 boy) normal
If it is assumed that 4 children are produced (2 male and 2 female), the father is a carrier (abnormal X, he has disease), and the mother is normal, the STATISTICAL expectation is for:
2 girls with disease
2 boys normal
This does not mean that children WILL necessarily be affected; it does mean that EACH child has a chance of inheriting the disorder or of being a carrier.




14. SEX-LINKED RECESSIVE 
SEX-LINKED RECESSIVE Information:

Definition:
An abnormal gene on the X chromosome from each parent is required to cause the disease in females since the female has 2 X chromosomes. In males there is only one X chromosome, therefore, a single recessive gene on the X chromosome will cause the disease. (Note: Although the Y chromosome is the other half of the XY gene pair in the male, the Y chromosome is only a portion of the X chromosome and doesn't protect the male. Therefore recessive genes on the X chromosome of the male will be expressed. This is seen in diseases such as hemophilia and muscular dystrophy.)

BACKGROUND:
The inheritance of genetic diseases, abnormalities, or traits is described by both the type of chromosome the abnormal gene resides on (autosomal or sex chromosome) and by whether the gene itself is dominant or recessive.

Autosomally inherited diseases are inherited through the non-sex chromosomes, pairs 1 through 22. Sex-linked diseases are inherited through one of the "sex chromosomes", the X chromosome (diseases are not inherited through the Y chromosome).

Dominant inheritance occurs when an abnormal gene from ONE parent is capable of causing disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair.

Recessive inheritance occurs when BOTH matching genes must be abnormal to produce disease. If only one gene in the pair is abnormal the disease is not manifest or is only mildly manifest; however the disease can be passed on to the children.

STATISTICAL CHANCES OF INHERITING A TRAIT:
For an X-linked recessive disorder:

If only the mother carries the gene and the father is normal, all of the female children will be normal (50% with 2 normal chromosomes and 50% carriers), one half of all the male children will exhibit the disease, and one half will be normal. The recessive gene is expressed in the male because there is not another X to counteract it, only the Y (which determines for maleness).
If only the father caries the recessive gene, all of his daughters will be carriers and all of his sons will be normal
If both the mother and the father carry the abnormal gene, then STATISTICALLY out of 4 children 1 daughter will have the disease (two recessive genes on the X chromosome), 1 daughter will be a carrier, 1 son will have the disease (one recessive gene on the X and a Y chromosome) and the other son will be normal. In other words, 50% of the children (boys and girls) will be affected and 50% normal.
In other words, if it is assumed that 4 children are produced (2 boys and 2 girls), the mother is a carrier (one abnormal X but no disease), and the father is normal, the 

STATISTICAL expectation is for:
1 boy normal
1 boy with disease
1 girl normal
1 girl carrier without disease

If it is assumed that 4 children are produced (2 boys and 2 girls), the father is a carrier (1 abnormal X, he has the disease), and the mother is normal, the STATISTICAL expectation is for:
2 boys normal
2 girls carriers without disease
If it is assumed that 4 children are produced (2 boys and 2 girls), the father is a carrier (1 abnormal X, he has the disease), and the mother is a carrier (one abnormal X but no disease), the STATISTICAL expectation is for:
1 girl with disease
1 girl carrier without disease
1 boy (abnormal X) with disease
1 boy normal

This does not mean that children WILL necessarily be affected; it does mean that EACH child has a chance of inheriting the disorder or of being a carrier.


15. Autosomal recessive 
Autosomal recessive Information:

Definition:
An abnormal gene on one of the autosomal chromosomes (one of the first 22 "non-sex" chromosomes) from each parent is required to cause the disease. People with only one abnormal gene in the gene pair are called CARRIERS but since the gene is recessive they do not exhibit the disease. Both parents must be carriers in order for a child to have symptoms of the disease; a child who inherits the gene from one parent will be a carrier.

BACKGROUND:
The inheritance of genetic diseases, abnormalities, or traits is described by both the type of chromosome the abnormal gene resides on (autosomal or sex chromosome) and by whether the gene itself is dominant or recessive.

Autosomally inherited diseases are inherited through the non-sex chromosomes, pairs 1 through 22. Sex-linked diseases are inherited through one of the "sex chromosomes", the X chromosome (diseases are not inherited through the Y chromosome).

Dominant inheritance occurs when an abnormal gene from ONE parent is capable of causing disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair.

Recessive inheritance occurs when BOTH matching genes must be abnormal to produce disease. If only one gene in the pair is abnormal the disease is not manifest or is only mildly manifest; however the disease can be passed on to the children.

STATISTICAL CHANCES OF INHERITING A TRAIT:
For an autosomal recessive disorder: When both parents are carriers of an autosomal recessive trait there is a 25% chance of a child inheriting both abnormal genes (developing the disease). There is a 50% chance of a child inheriting one abnormal gene (being a carrier).

In other words, if it is assumed that 4 children are produced, and both parents are carriers (neither exhibits any disease), the STATISTICAL expectation is for:

1 child with 2 normal chromosomes (normal)
2 children with 1 normal and 1 abnormal chromosome (carriers, without disease)
1 child with 2 abnormal chromosomes (has the disease)
This does not mean that children WILL necessarily be affected; it does mean that EACH child has a one in four chance of inheriting the disorder and a 50:50 chance of being a carrier.




16. Genetic counseling and prenatal diagnosis 
Genetic counseling and prenatal diagnosis 
Information:
For over 4000 years, certain human abnormalities have been noted to run in families but the "WHY" of the observations did not become apparent until the advent of modern genetics and the recognition of how genetic information is transmitted. Before then one only heard the admonition, "it's in the blood" (thought to refer more to bloodline rather than some abnormal element in the blood).

Present day medicine has recognized how genetic diseases are inherited based on an understanding of the nature of DNA, genes, and chromosomes. Scientists are presently trying to "map" the chromosomes, to determine the location and function of all of the millions of genes in each chromosome. This will ultimately help in treating genetic disorders.

However, until science has the ability to treat some of the more disastrous and ultimately fatal genetic disorders the best remaining recourse is prevention. Prevention of genetically transmitted disease can consist of major choices: abstinence from pregnancy, artificial insemination, prenatal diagnosis, and termination of affected pregnancies.

Prenatal diagnosis involves testing fetal cells, amniotic fluid, or amniotic membranes to detect fetal abnormalities.

Genetic counseling (and prenatal diagnosis) provides parents with the knowledge to make intelligent, informed decisions regarding possible pregnancy and its outcome. Based on genetic counseling some parents, in the face of possibly lethal genetic disease, have forgone pregnancy and adopted children while other have opted for artificial insemination from an anonymous donor who is not a carrier of the specific disease.

Many diseases transmitted as a single gene defect can now be diagnosed very early in pregnancy. Because of this some parents have elected to become pregnant and then, early in the pregnancy, had the disease status of the fetus determined. The pregnancy is continued if the fetus is disease-free. Parents who decide to continue the pregnancy with a defective fetus may be able to better prepare to care for the infant by being informed about the disease in advance.




17. Chromosome 
Chromosome Information:
Humans have 46 chromosomes. There are a total of 23 pairs of chromosomes or 46 total chromosomes. All of the body's genes are contained within these 46 chromosomes.

Two of the chromosomes, the X and the Y chromosome, determine sex and are called the SEX CHROMOSOMES. Females have 2 X chromosomes and males have 1 X and 1 Y chromosome. The Y chromosome determines the male sex but does little else.

The remaining 44 chromosomes are called AUTOSOMAL CHROMOSOMES. Chromosomes exist in pairs. For convenience, scientists have numbered the autosomal chromosome pairs 1 through 22. The X and Y chromosome are the 23rd pair.

Each parent contributes one half of each pair or 23 chromosomes to their child, 22 autosomal and 1 sex chromosome. Females always contribute an X chromosome to the child while a male may contribute an X or a Y. Therefore, it is the male that determines the sex of the child.





18. Gene 
Gene Information:
Genes are the smallest units of heredity. The information from all the genes, taken together, makes up the blueprint or plan for the human body and its functions. A gene is a short segment of DNA which is interpreted by the body as a plan or template for building a specific protein. Genes reside within long strands of DNA which in turn make up the chromosomes. Some diseases, such as sickle cell anemia, can be caused by a change in a single gene (one out of the millions of genes which make up the plan for the entire human body).

Genes are arranged in order along the DNA strand within the chromosome (similar to beads on a string). Matching genes from each parent exist on matching chromosomes and matching positions along the DNA within the chromosome. These genes are paired, one from the mother and one from the father. Genes are described as DOMINANT or RECESSIVE. DOMINANT means that one gene in the gene pair is able to control the trait which that gene pair codes for. RECESSIVE means that both genes in the gene pair are necessary to control the trait.