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Such a pictorial representation of all the chromosomes of an organism is called an idiogram
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Certain abnormalities, such an extra chromosomes or piece of a chromosome, can be detected.
Since 1969, special techniques have been developed to stain the human chromosomes with fluorescent dyes after various treatments. With different treatments, the chromosomes show different banding patterns (alternating stained and unstained regions).
The banding pattern helps in identifying the various regions of individual chromosomes. Four kinds of banding patterns of chromosomes are so far known. These are named Q – qui-nacrine, G – giemsa, R – reverse of giemsa and C – constitutive heterochromatine.
Cytogenetic methods helps in:
1) Studying the karyotypes of an organisms;
2) Making more precise the human number of chromosomal sets, number of chromosomes and morphology of separate chromosomes for diagnosting the chromosomal diseases;
3) Making up the genetic cards of chromosomes;
4) Studying the genome and chromosomal mutations.
Method of determination of sex-chromatin or Barr body. Human a mammals somatic cells consist of two X-chromosomes, one of out form block of chromatin which is well visible in special cultivation in interkinetic nucleus. It is a condensed inactive X-chromosome of females, which was discovered in 1949 by Barr. He examined nucleus of neurons of female cat’s brain.
Later similar bodies was discovered in human. It is called Barr body or sex – chromatin (X-chromatin). Foetal skin cells are always sloughed off into the amniotic fluid. Microscopic study of these cells or check cells can reveal the sex of the unborn child. A dark-staining mass, called sex chromatin, or Barr body, is present in contact with the nuclear envelope in the cells of a female. The cells of male lack Barr body.
Knowledge of the sex of very young foetus can help in predicting the occurrence of sex-linked genetic disorders.
Sometimes it necessary for judicial – medical examination or experts in questionable cases of determination of sex, if defect in structure of external sex organs occurs.
Amniocentesis. It is foetal analysis or Prenatal diagnostic technique to determine the genetic disorder. The fetus develops in the amniotic sac, it is surrounded by amniotic fluid that fills the amniotic cavity. At an early stage of pregnancy (16-17 weeks), a small amount of amniotic fluid about 10 ml is drawn by drawn by passing a special surgical syringe needle (without causing any damage to the foetus) through the abdominal wall and uterine wall into the amniotic sac containing amniotic fluid. The amniotic fluid contains cells that have sloughed off the foetus skin; these cells can be cultured in the laboratory. They may be examined for protein or enzyme alterations or deficiencies, metabolic disorders such as PKU, sickle-cell anemia, DNA changes, and chromosomal abnormalities.
In case of any serious congenital defect termination of pregnancy is advised. Amniocentesis is often misused to determine the sex of the child so as to abort the female foetus.
Because amniocentesis is complicated and costly, it is primarily used in high-risk cases.
A new technique, named chorionic-villus sampling (CVS) can be done during the light to eighth to tenth week (8-10 week) of pregnancy when abortion is safe for the women. That is earlier than amniocentesis. The chorion is a membrane layer surrounding the foetus, and it consist entirely of embryonic tissues.
A chorionic villus tissue sample may be taken from the developing placenta through the abdomen (as in amniocenteses) or via the vagina using biopsy forceps or a flexible catheter, aided by ultrasound. Once the tissues sample is obtained, the analysis is similar to that used in amniocentesis.
Ultrasound examination is using of US-rays for detection of foetus and its envelopes. On 5th week of pregnancy can be seen envelopes of an embryo, on 7th week – an embryo, in end of 6th week – heart beating, on 12 – 20 week – defects of development, such as anencephaly, defects of bonds, neural tube, localization of placenta, diagnosis of twins.
VI. Biochemical method is a study of biological liquids such as blood, urine, amniotic fluid, liquor or spinal fluid, that allow to reveal the breakage of metabolism with help of chemical analysis.
There are 300 inborn metabolism or gene disease was discovered by biochemical methods.
Biochemical method is useful for genetic counseling of couples at risk for having children with genetic disorders, gene diseases.
Molecular genetics is a specific relationship between genes and enzymes, historically embodied in Beadle and Tatum’s “One gene - one enzyme” hypothesis, which states that each gene controls the synthesis or activity of a single enzyme. Since we know that enzymes may consist of more than one polypeptide and that genes code for individual polypeptide chains, a more modern title or description for this hypothesis is the “one gene - one polypeptide” hypothesis.
Many human genetic diseases are caused by deficiencies in enzyme activities. Most of these diseases are inherited as recessive traits.
Cause of gene diseases is breakage of metabolism. As known proteins may be structural; proteins, having specific functions like transfer of oxygen, protein-hormones and protein enzymes. Protein- enzymes are catalysators and participants of all biochemical reactions in the cell.
Therefore the absence or inactivity of the enzyme is due to the absence of the normal form of the gene that controls the synthesis of the enzyme.
Accumulation of derivatives or intermediate products of metabolism of metabolism in blood, urine, amniotic fluid and other occurs, which damages the brain and other organs and causes the disease.
Lack of the enzyme is due to the abnormal recessive gene. This mutant gene controls the synthesis of the “wrong” enzyme. It is also called enzymopathy.
General scheme of enzymopathy:
Mutant gene → changing nonfunctional enzyme → breakage of chemical reaction → absence of any substrates (impossible synthesis) → accumulation of derivatives in the urine, blood, secret of bronches, amniotic fluid and other biological liquids
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non-function of organs, damage the brain, liver, kidney…
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disease (suffers whole organism)
The multiple effect of a single gene is called pleiotropy.
For example, phenylketonuria (PKU) Cause:
1. Recessive mutation of gene on chromosome-1 which control the synthesis of enzyme phenylalanine hydroxylase.
2. The absence of that enzyme activity prevents the conversion of the amino acid phenylalanine to the amino acid tyrosine. Phenylalanine is one of the essential amino acid.
3. Phenylalanine, some of it changes into phenylpyruvic acid and metabolic block in the pathway occurs.
4. Phenylalanine accumulates in the tissues, accumulation of phenylketones and other derivatives in urine, blood and other fluids of an organism.
5. This substance drastically affects the cells of the central nervous system and produces serious symptoms: severe mental retardation, a slow growth rate, and early death.
6. Disease is called phenylketonuria (PKU). PKU homozygotes develop normally on low phenylalanine diets.
Diagnosis of metabolic disorders is important, because the biochemical indexed appears early, than chemical symptoms.
In PKU the chemical analysis of the urine for determination of phenylpyruvic acid and other derivatives is helpful by add FeCl2- iron chloride to urine which results changing colour of urine into green. It is qualitative reaction. This method used when child two month of life.
Protein analysis of amniotic fluid gives information about the enzymes present in it. This information can help in detecting inborn metabolic disorders, which are caused by absence or inactivity of specific enzymes.
Knowledge of metabolic disorder in a foetus will enable the parents to arrange for treatment after birth or to decide an abortion.
Inborn errors of metabolism (“gene” diseases)
a) defects of amino acids metabolism:
Phenylketonuria (PKU) – is an inborn error of metabolism. PKU occur in about 1 in 12000 births. PKU is most commonly caused by a recessive mutation of a gene on chromosome 1. The homozygous recessive individual lacks the enzyme phenylalanine hydroxylase needed to change one amino acid, phenylalanine, to another, tyrosine. The absence of that enzyme activity prevents the conversion of the amino acid phenylalanine to the amino acid tyrosine. Phenylalanine, phenylketones and other derivatives in urine, in the tissues accumulate, and some of it into phenylpyruvic acid which damages the brain and causes the disease.
Accumulation of derivatives affects the cells of the central nervous system and produced serious symptoms: severe mental retardation, a slow growth rate, and early death.
Albinism is caused by an autosomal recessive mutation, and individuals must be homozygous for the mutation to exhibit the condition.
Albinism is characterized by lack of dark pigment melanin in the skin, hair and iris. It is caused by the absence of the enzyme tyrosinase which is necessary for the synthesis of the pigment melanin from dihydroxyphenylalanine. The gene for albinism (a) does not produce enzyme tyrosinase, but its normal allele (A) does. Thus, only homozygous individual (aa) is affected.
Albinism by itself is not a disability. However, an albino is susceptible to eye disorders due to the damaging effect of bright light.
Since no melanin can be produced albinos have white skin, white hair, and red eyes (because of a lack of pigment in the iris). Melanin absorb light in the UV range and is important in protecting the skin against harmful UV irradiation from the sun. Albinos therefore are very light-sensitive.
Alkaptonuria is an inborn metabolic disorder produced by the action of a single gene. Its symptoms include blackening of urine on exposure to air and darkening of certain cartilages.
Urine of alkaptonuric person contains homogentisic acid, which spontaneously combines with oxygen to form a black pigment. This pigment slowly deposits in the cartilages of ears and nose. It also causes mild arthritis.
In normal persons, a liver enzyme homogentisate oxidase catalyzes the breakdown of homogentisic acid to compounds that enter. Krebs cycle to produce carbon dioxide and water. The alcaptonurics are unable to breakdown homogentisic acid because of the absence or inactivity of the enzyme needed for this purpose. Lack of the enzyme is due to the absence of the normal form of the gene that controls the synthesis of the enzyme. Hence, homogentisic acid accumulates and is excreted in the urine.
Дата публикования: 2015-09-17; Прочитано: 1193 | Нарушение авторского права страницы | Мы поможем в написании вашей работы!
