3.6 Secrets of DNA to Help You Live Long

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This chapter is technical but important, especially for students who wish to go to university, or to study for nursing, medical doctor or other sciences. Reading and rereading may up your IQ, TOEFL, SAT or MCAT scores.
Chapter 6: Genetic Testing - 03 Aug. 2021 Update

You started as a newly created cell from single cells – Mother’s ovum and Father’s spermatozoon - combining. Then the new cell divided to 2, to 4, and so on; now the very same You are a 40-trillion cell offspring of the original new cell. The cells combining have assumed a number of tissue shapes but all single cells have a similar basic structure – cytoplasm surrounding the central nucleus. Every human cell except the gametes (spermatozoa or ova) has 23 chromosome pairs, which identify the individual you as You. One of each pair is from your mother and the other from your father. If with a mate you reproduce a new individual offspring, its cells will get one each of your 23 chromosome pairs.

   Chromosomes are long molecules made of DNA strands.

Above is a schematic of a single (found only in a nuclei of sperm or ova)  and paired chromosomes (found in the nuclei of all other body cells). Each chromosome pair has many points (singular, point, or locus; plural, locii) of inheritable DNA, each DNA point called a gene. Although a particular chromosome and its pair are very alike in each gene pair, one gene of the pair is slightly different from the other gene due to spontaneous cross-over rearrangement or mutation. Of the 23 chromosome pairs, one pair is the sex chromosome – xx shape in female and xy in male. The chromosomes are numbered as pairs in order of larger to smaller size; the sex pair is #23 - the smallest.

   Each chromosome has about a thousand genes at specific points along its length and each gene produces a specific protein based on its amino acid protein-code (DNA/RNA triplets; see later) and each protein is either used structurally or as an enzyme. (An enzyme speeds a chemical reaction without being consumed in it.) All the genes that could be contained at all of the gene points of the 46 chromosomes in the 23 pairs in a human cell are called the genome. The human genome is presently estimated to contain 23,000 amino acid protein-code genes. (Averaging out of several estimates) Your genes have a strong influence in determining  your structure, function, and consciousness. But keep in mind that the influence of the environment is the final determinant of these qualities. One is not superior to the other; it is the interaction of genes with environment that makes the You who you are.

   You may note that with 23 chromosomes holding 23,000 gene sites, it averages 1000 genes per chromosome.

   “DNA” is for “deoxyribose nucleic acid.”  First get a look at the “Ribose”   

It is  a 5-point cyclic ring structure, in which an apex oxygen (O) atom and four carbon (C) atoms at the angle-points form the 5-side ring, and the 5th C atom (5') out of the plane of the ring. To number the C atoms, start at the apex O atom and begin clockwise counting with the first C atom to your right, ending up with the 5th C atom on your left as the 5'. In the figure, the C letters are not written-in but are numbered except 1' and 4' and are assumed at each apex of the ring structure except where the “O” is placed. (The structure of Ribose you see above is a typical cyclic carbohydrate structure that you met up with in the Carbohydrates nutrition chapter: 5-sided with a top apex Oxygen atom and a Carbon atom counting system that is clockwise starting to your right. The famous Fructose mono sugar will be seen to exist as such a molecule.)

Now look at “deoxyribose”.

It is the same as ribose except it has lost the OH of ribose in the cyclic structure under the C-position 2, replacing it with an H. The loss of the O gives the “DEOXY-”.

Deoxyribose supplies the “D” to DNA but the next structural part of DNA goes silent. It is “phosphate” (-PO₄^3-), a 3-negative electrically charged ion radical that serves as link between successive deoxyribose segments in DNA molecules.

      O-
 O=P –O–H2C5 (phosphate link)

      O-

In the figure above, the phosphate link of successive deoxyribose molecules is through the C-3 atom of one deoxyribose to the C-5 atom of the next connecting deoxyribose. In a long, twin-strand DNA molecule the phosphate linkage on one strand starts with a C position 5 linkage and links in the sequence, e.g., 3rd C-5th C-3rd C-5th C, till end of strand while the opposite-side strand starts at the C position 3 linkage and links in sequence, e.g., 5th C-3rd C-5th C-3rd C, till its end. (Like left-handed, right-handed ideas) This orientation of the twin strands, with the first linkage that starts off a DNA C position-5 on one strand and a C position-3 on its connected strand is called “anti-parallel” orientation to emphasize that each one of the twin strands in a DNA molecule is not the exact image sequence-structure of the other but is its complementary mirror image.

The Purine and Pyrimidine Bases

The most important part of DNA is the bases, which are chemical structures called purines or pyrimidines. (“Base” is because the nitrogen N atoms and unsaturated double-bond =O oxygen atoms of purine or pyrimidine molecules are alkaline due to their attraction for H+. A base, being the opposite of an acid, attracts and holds onto H⁺).

Below you see the purine, guanine, linked to the pyrimidine, cytosine, and then the purine, adenine, linked to the pyrimidine, thymine : these are fundamental linkages of the genetic code which hold the DNA double-strand together and also allow one strand to reconstruct its pair in reproduction. And note the linkages are through hydrogen bonds, which are loose linkages easily broken and just as easily re-formed.

Use magnifier for inspection

The purines of DNA and RNA are Adenine and Guanine and the pyrimidines of DNA only are Thymine and Cytosine. (Shown in the pairs above) In RNA (ribose nucleic acid) the pyrimidine Uracil replaces the similar structure Thymine.

In DNA, the “base pairs” are Adenine and Thymine (A&T) and Guanine and Cytosine (G&C). In each pair, one molecule is a purine and the other a pyrimidine. Also note (in the above) that both the purines, Adenine and Guanine, fit each one’s respective pyrimidine pair mate in the jutting-out NH2 of Adenine paired with the key-in-lock accepting double bond, =O of Thymine and the =O of Guanine paired with the jutting-out NH2 of Cytosine.

Above you see the twisted double helix, which is the actual structure of each chromosome.



The blue and red horizontal half steps in the ladder show the base pairs (visualize blue for a purine, red for a pyrimidine) in which the purine, guanine, paired with the pyrimidine, cytosine, or the purine, adenine, with the pyrimidine, thymine, with the purine-pyrimidine holding the inner sides of the double strand together by the weak H bonds.

   The long DNA molecule of a chromosome allows one chromosome length to contain approx 85-million base pairs. So in the above figures you are looking at merely a tiny segment of the twisted double-strand, and the attached bases of the strand are facing in an inward direction the matching strand with complementary bases, as indicated in the double stranded DNA segment.

The sequence of bases in the geometric figure from above downward is shown in the column below on your left (T thymine, A adenine, G  guanine, C cytosine).

T………….A

A………….T

G………….C

C………….G

Note the interesting fact of the limitation of the base pairing. At each vertical segment level, wherever the pyrimidine T occurs as base the purine A must be its pair mate, wherever purine A occurs as base the pyrimidine T must be its pair mate; then, wherever the purine G occurs as base the pyrimidine C must be its pair mate and wherever the pyrimidine C appears as base the purine G must be its pair mate. This will begin your knowledge of the famous genetic amino-acid, protein code. The limitations that force these specific pairings are the structural complementarity (the fitting into each one's structure) of the specific purine with the specific pyrimidine molecule and also within that size balance, the complementarity of the NH2 and the double bond, i.e., z=O, previously mentioned.

   Focus now on the 4-base pair segment of a DNA molecule, an actual part of a gene, shown in the figures. The strands are the deoxyribose-phosphate linked structure, and the base pairs face each other on the inside of the structure like steps in a spiral staircase. Now if you direct attention to the base pairs you will see the relationship between each pair, already stated. Wherever an adenine (A) is attached to one strand, a Thymine (T) is attached to the opposing strand. And a Guanine (G) with a Cytosine (C). (But not an A with a G or not a T with a C)

The bonding (Indicated by the bridging dots in the T…., A…., G…., C…. columns) between the A & T and the C & G is between an H atom of one of the base pairs and the O or N atom of the other base pair.

   These are “hydrogen bonds”, and they occur because the =O and the N atom of –NH2, and the apical N atoms of the purine and pyrimidine have an attraction for the single electron in orbital about the H atom and so a molecule like Adenine naturally attracts a molecule like Thymine and vice versa, and similarly Guanine to Cytosine. The H bonds are weak, easily split, so DNA is a molecule easily split into its single strands and just as easily recombined to become double-strand in the same sequence, which is useful in replication of chromosomes.

Structure of DNA. (Slide the figure to your left to complete the right side view)

Four different purine or pyrimidine bases, adenine (A), thymine (T), cytosine (C), and guanine (G), are assembled on a sugar phosphate backbone in the double-stranded DNA helix. The sugar phosphate base is called a nucleotide.  Many nucleotides make up the DNA strand.

  But check it on Internet.

    At this point to sum up about the DNA molecule:

   Single, long, twisted DNA molecules are the structures of chromosomes; the 23 pairs of the molecules are in every human cell nucleus except from spermatozoon and ovum, which carry only one each of the two 23`s specific to male or female that make a blueprint of each human individual.

   The DNA molecule of chromosomes is made of anti-parallel double strands, which twist about each other to form the famous “double helix”, made of deoxyriboses that are linked by phosphate and hold purine-pyrimidine linked base pairs as inner steps of the helix.

   In DNA the steps of the staircase, or ladder, consist of adenine of one strand linked by weak H bonds to thymine of the other strand, or guanine of one strand linked similarly to cytosine of the other strand. The A&T and G&C sequence order makes a genetic protein-code.

Replication of the Chromosomes and DNA

The figure shows DNA replication by splitting (unzipping).

  In 1, you see the intact DNA molecule (imagine the twisted double-helix untwisted to look like a straight ladder) with the H-bond linked base pairs as rungs. The H bonds of A&T and G&C that hold the two strands together are weak, as chemists discovered by heating the DNA to 95⁰ C which causes the double strands to separate but allows the rest of the molecule to remain intact. Even more interesting, when the separated strands of DNA cool below 55⁰ C, the DNA spontaneously regenerates to double-strand DNA in exact base pair sequence structure as before the heating! The explanation is that each cooling, single strand of heated DNA, seems to direct re-synthesis of its normal double-stranded structure because the H bonding of bases (A,G,C,T) causes each to attach only to its complementary base (i.e., the A attaches only to T; the T attaches only to A, the G attaches only to C, and the C attaches only to G).

   In 2, above, you see the DNA unzipped, with the DNA molecule, separating the double strand into two single strands. This unzipping starts at top (“top” or “bottom” refers to anti-parallel-strands orientation, in C5 to C3 direction on one strand and C3 to C5 in the other) of the DNA molecule and proceeds along its length to the bottom.

   In 3, above, you see the construction of a new DNA by new bases (in blue to show new) attached to an unzipped single strand which acts as a template for the new DNA molecule, and this actually starts while the unzipping is going on, just behind it. The enzyme DNA polymerase speeds construction of a new complementary DNA strand for each unzipped DNA strand. This explains the exact replication of chromosomes during reproduction – the formation of the reproductive cell –; it is based on the complementarity of the base pairs; the attraction of A for T, and of G for C.

   Keep your mind focused on DNA’s two functions: 1) To pass on the genetic code in the nuclear DNA to its offspring cells; and 2) to direct the production of specific protein structure by the millions of genes in a 23-pair chromosome set.

Ribose Nucleic Acid (RNA)

Ok So far I have centered on the DNA – the very long double-strand twisted molecule of deoxyribose sugars linked by phosphate and with purine-pyrimidine segments that lock in place each of the two strands by inside central A-T, G-C hydrogen bonding. The DNA are the chromosomes, which are located only in the cell nucleus, and have as one main function making nucleic acid copies to carry on an individual’s genetic code in future offspring cells.

   DNA's second main function is to direct making a protein based on the gene pattern. This needs a change from the double-strand nucleic acid molecule to a single-strand, which also involves a change of the strand's structure from deoxyribose sugar to ribose (See Ribose and Deoxyribose structures at start of chapter) and a replacement of the Thymine in double-strand DNA by the very closely structured Uracil in the single-strand RNA. This is called transcription.

   Transcription is done by the DNA's unzipping but not re-zipping, and the result is that the offspring are single-strand RNA (Ribose Nucleic Acid) whose purine-pyrimidine base sequence is complementary to the purine-pyrimidine base sequence of each unzipped strand of the DNA that makes the RNA complement copy.

• At this point a reader has enough information to understand what is called The Central Dogma based on 50+ years of DNA research since James D. Watson and Francis Crick first realized the double strand twisted helix structure of DNA being the key to gene transcription: The DNA undergoes transcription to the RNA in its complementary image and the RNA via structures called ribosomes that assemble amino acids according to the genetic code translates the amino acid sequences into proteins; it explains human individuality and diversity in that the gene-product proteins, acting as enzymes or used as structural elements, produce the individual in mind and matter.
• To carry out The Central Dogma, the DNA splits (same as replicates) and then, assisted by the enzyme “RNA polymerase”, the DNA “anti-sense” (the strand of DNA that will produce a code in the RNA that makes sense in making a protein) strand serves as template on which single-stranded RNA gets constructed.
•   If we take a DNA strand as template for RNA; then, at each level of the DNA where there is the pyrimidine Thymine, the purine Adenine clicks into place opposite; and where there is Adenine, a Uracil clicks into place [Recall that Uracil is the Thymine-in-DNA-substitute in RNA]; and where there is Guanine, a Cytosine clicks into place; and where there is Cytosine, a Guanine clicks into place. Note that with RNA we no longer speak of “base pairs” because RNA is a single strand with single bases attached at successively stepped ribose Carbon atoms along its length
•   Each DNA replicates its RNA copy. First line RNA copy is “first transcript messenger RNA”. The process is “transcription”.
• Let’s focus on first transcript messenger RNA just off the DNA assembly line. It is single-strand ribose phosphate backbone with a purine-pyrimidine base (A, U, G or C) at each successive level attached to C position 1 in the ribose molecule. The order of successive base attachment might seem random to someone who does not know there is a genetic amino-acid protein construction code involved.
•   What is the code? Proteins are constructed of amino acid building-blocks to make polypeptides (chains of amino acids linked by each amino acid's NH2 and COOH ends to the next one). A protein is a large polypeptide. The RNA molecule assembles the amino acids on metaphoric assembly line ribosomes to make particular proteins via the code. The genetic code translates triplet (a sequence of 3 successive purine-pyrimidine bases on an RNA molecule) of the 4 bases. (In RNA: Adenine & Uracil and Cytosine & Guanine.) into coding for each one of the amino acids in the code. If you are a math expert, you might know that if you have 4 objects to arrange in groups of 3 each, the maximum number of combinations of 3 for the 4 objects is 4³, or 4 x 4 x 4 = 64. So for the bases in sequence along the RNA ribose-phosphate backbone, it means there are 64 possible triplet combinations (bases in a row, e.g., AGU, UAG, CAC, …, …, …..). And the 64 base triplets must encode the 20 different human amino acids that make human proteins. So each of the amino acids is encoded by more than one triplet combination. (But a particular triplet can only encode a particular amino acid and no other) For example, in the actual genetic code, the simplest amino acid, glycine, is encoded by any one of the 4 triplets: GGU, GGC, GGA and GGG. None of these triplets encodes for any other amino acid.
• With an idea of this code, let us now return to the messenger, the mRNA (messenger RNA) just off the DNA template assembly line. This is a hugely long molecule, like the chromosome it came from. It needs to be processed before it can be used to produce protein.

 Messenger RNA: In the upper piece below (pre-messenger RNA),

focus attention on Exons, Introns and the green UTR’s (UnTranslated Regions). The pre-mRNA (topmost in the figure) is one larger segment of smaller segments of purine-pyrimidine base groups copied off its DNA. It is not ready to be coded because the intron segments insert between the exxon code and block the gene code from becoming translated into its amino-acid sequence. The introns must be excised and the exxons connected up so that the stretches of base sequence can become a meaningful code to make functional genes. So, the next stage to process the “raw” mRNA is to take a metaphoric scissor (endonuclease enzyme) to cut out the introns and connect up the exons to make functional genes.

   The endonuclease is the enzyme that acts like the scissors and the RNA polymerase is the enzyme that pastes together the adjacent exons and forms the working genes. Also note the UTR’s at the beginning and end of the gene which signal the start and stop of a functional gene much as the first capital letter signals the start of a sentence and the final period signals the end of the sentence.

   The processed mRNA passes from cell nucleus into cell cytoplasm where it is acted on by a cell structure called “Ribosome” to assemble the amino acids coded for combination into a specific “polypeptide” (protein). This is a simplified explanation of protein synthesis from the gene.

Inheritance of Genes from Parent to Offspring
Inside the nucleus of each human cell are 23 pairs of chromosomes. (Exception are the sperm and ova cells which contain one of each pair of the 23-paired chromosomes) Each one of a pair grossly under the light microscope resembles its pair mate in size and shape with one pair an exception, the sex chromosomes in males, where one of the pair looks like an x and the other of the pair like a y.

  When a human cell produces a reproductive cell (spermatozoon or ovum), each one of the x & y sex chromosome pair separate – one sex chromosome of a pair going to one offspring reproductive cell and the other sex chromosome to the other offspring reproductive cell, and the usual chromosome number (46 as 23 pairs in human) is halved (23 singlets) in a sperm or an ovum. When a sperm fertilizes an ovum at conception, the cells fuse and the chromosome count is restored to 46 as 23 pairs. So each sex chromosome of a chromosome pair consists of one pair-mate from father (x or y) and the other from mother (one of the 2 x's). One other point: the 23 single chromosomes each of an original chromosome pair get "scrambled" in the passing to each different sperm or egg. No sperm exactly resembles another sperm of its clone. This is very important for individuality of humans.

    In inheritance of genetic characteristic, the chromosome identifying number is the first key. Up to 1,000 genes are in each chromosome of the 23 chromosomes and each gene on a chromosome differs from other genes on that chromosome. Also each of the 23 chromosomes has a mate (One chromosome mate of the pair from father, the other from mother). At the same site on it and on its mate are matching gene sites, known as gene loci. In these sites are located matching gene structures (called “alleles”), for example, the gene structure that produces the melanin pigment that gives a person brown eyes rather than blue eyes. To take the example further, a brown-eyed person must have at least one gene of the eye color pair that produces melanin brown eye pigment and he could also have both pairs of genes producing melanin. If he has the both genes producing melanin, all his sperm will contain the brown eye gene and all his offspring will be brown-eyed no matter what color eyes his mate has because only a little melanin in the eye gives the brown color. This is an example of a dominant gene: even a half dose from one parent gives the physical effect. Blue eyes are the result of a chromosome pair each of which contains a gene defective for the melanin-producing enzyme. Both parents may actually be brown-eyed but if they are the type of brown eyes that comes from a partial dose of the melanin-producing gene each parent could pass a defective-for-melanin gene to offspring leading to a blue-eye baby with both genes in the pair being defective for melanin-producing enzyme in the the eyes, giving the blue-eye effect. We say breeding pure for blue eyes.

   The above example is single gene effect – eye color is typical. But most genetic-related illnesses – like schizophrenia – are the result of many genes determining one characteristic (polygenic) plus environmental influence. And sometimes the genes are on different chromosomes.

Mitochondrial Inheritance

Each cell has sub-cellular bodies in its cytoplasm that have the important function of oxidation to produce ATP (adenosine triphosphate) packets of energy. These are called mitochondria. A mitochondrion has its own DNA – a ring of 37 genes and 16,569 base pairs. Because a sperm contains practically no cytoplasm it does not carry mitochondrial DNA to offspring. Mitochondria all come from cytoplasm of Mother’s ovum so mitochondria inheritance comes from the mother only. It is a way of tracing evolution through the female. Some muscular and neurological inherited diseases are mitochondrial in origins.

How much does a gene affect an animal's (humans too) behavior is a big question argued between social evolutionists (aka sociobiologists) and environmentalists. Of course both factors combine to affect some behaviors. But recent evidence from lower forms suggest that a gene may have a stronger affect than previously thought. For example

Feeding behavior of the roundworm Caenorhabditis elegans depends on the level of activity of a neuropeptide receptor gene.

In one strain individual worms graze in isolation (left), whereas in another strain individuals mass together to feed.

The difference between social and solitary worms is caused by a single amino acid substitution in a single gene, a member of a large family of genes involved in signaling between neurons. This gene, npr-1, encodes a neuropeptide receptor. Neuropeptides have long been appreciated for their roles in coordinating behaviors across networks of neurons. For example, a neuropeptide hormone of the marine snail Aplysia stimulates a complex set of movements and behavior patterns associated with a single behavior, egg laying. Mammalian neuropeptides have been implicated in feeding behavior, sleep, pain, and many other behaviors and physiological processes. The existence of a mutation in the neuropeptide receptor that alters social behavior suggests that this kind of signaling molecule is important both for generating the behavior and for generating the variation between individuals.

Genetic Testing and the Human Genome

Genetic testing has 3 uses:

1) Diagnosing difficultly diagnosed disease. (E.g., viral myocarditis is a difficult to diagnose inflammation of heart muscle, where the accuracy of diagnosis can mean life or death. Identifying the viral gene by its typical base-pair sequencing prevents wrong treatment and death)

2) Predicting deadly genetic disease in parent or in pregnant woman (e.g., Huntington’s chorea by genetic testing of parental DNA or amniotic fluid from the early pregnancy).

3) Treating or preventing genetic disease like Sickle Cell Anemia by identifying the gene that causes it.

In the RNA base sequences below, note an example of The Central Dogma. The double-stranded DNA transcribes to the single-stranded RNA that translates to the amino acids sequence that defines the particular protein. Note the two column headings “WILD TYPE” and “MUTANT” and beneath each heading in the 3 rows, the comparison of transcribing DNA, transcribed RNA and translated protein between WILD TYPE and MUTANT.  The “WILD TYPE” means as found in nature, ie, normal, healthy type. The “MUTANT” is change from WILD TYPE due to change in DNA caused by cosmic rays. We are looking at comparison of the same segment of one chromosome (allele locus, actually both maternal and paternal derived alleles) between normal healthy person and one born afflicted by Sickle Cell Anemia (SCA)

          Original DNA in Nucleus

  WILD TYPE (ß^A)                      MUTANT (ß^S)

ATG-GTG-CAC-CTG-ACT-CCT-GAG       ATG-GTG-CAC-CTG-ACT-CCT-GTG

TAC-CAC-GTG GAC-TGA-GGA-CTC      TAC-CAC-GTG-GAC-TGA-GGA-CAC

               Transcription from DNA to RNA

AUG-GUG-CAC-CUG-ACU-CCU-GAG    AUG-GUG-CAC-CUG-ACU-CCU-GTG

   Translation from RNA to amino acids - protein

                           WILD              /         MUTANT

 Met-  Val-  His- Leu- Thr- Pro Glu   / Met-Val-His- Leu-Thr-Pro-Val

Now look at comparison across the DNA row between Wild and Mutant Sickle Cell Anemia (SCA). Recall the capital letters ATGC stand for bases “Adenine”, “Thymine”, “Guanine” and “Cytosine”. Also see that the DNA in the just shown base triplet sequences has 2 rows because of its double strand and base triplet pairing. So the first base triplet pair, from left is ATG over TAC, and the next is GTG over CAC, and so on down the line to your right.

   First to notice in comparing DNA triplets, the normal Wild against the sickle cell Mutant, is how alike they both are: Until the final triplet base-pair (To your extreme right in the row), out of the 7 triplet base-pairs shown, the first 6 are exact copies of each other until the final triplet, which differs in that for the normal it is GAG over CTC and for the mutant it is GTG over CAC. (Underlining of the bases that differ)  And, focusing on this single difference of base pairs, we see it only involves the knock-over of the middle base pair A over T from the triplet GTC in the Normal into T over A in Mutant to cause the Sickle Cell Anemia.

   Looking at the RNA single-strand row (Note U in RNA replaces T in DNA), we see that after transcription (the lower set of bases in the RNA row, e.g., the starting AUG-GUG….), the RNA again only differs between normal and mutant in the change of the final GAG triplet into the GTG triplet.

   Looking at the Protein row (after “translation” of the code from the RNA triplets to the amino acids), we see the amino acid sequence that makes up the key segment of the red blood cell hemoglobin molecule (known as the ß-globin, or beta-globin). On the left for the normal wild type, the segment shows the amino acids Val(ine), His(tidine), Leu(cine), Thr(eonine), Pro(line), Glu(tamic Acid) while the Mutant Type that is afflicted by SCA shows the same amino acid sequence except that the last amino acid Glu(tamic Acid) in the line of the normal protein structure has been knocked out and replaced by Val(ine) in the mutant SCA.

   Here is the cause of Sickle cell Anemia, a disease that terribly afflicts millions and kills prematurely. Many thousands of years ago, visualize a spot in Africa and a cosmic ray striking a direct hit on the particular DNA in the chromosome that determines the ß-globin part of hemoglobin? And the hit knocks a Thymine and its paired Adenine base out of the natural position, spinning it around to upside down position so its anti-sense Adenine became Thymine and forming the RNA base triplet GTG instead of the normal GAG and translation to the amino acid valine  instead of glutamic acid  at the end of the ß-globin part of the hemoglobin molecule. This resulted in the mutant’s having a type of hemoglobin which still functions to pass oxygen to the tissues but is defective in that it collapses the red blood cell more easily if oxygen gets low in the tissues and which leads to Sickle Cell Anemia symptoms (Severe pain from clogged small arteries with broken red blood cell debris) and signs (severe anemia from destroyed RBC). This mutation in its impure form (from only one of the maternal/paternal chromosome pair; or so-called heterozygote) is compatible with apparent normality. It is only when one gets a double dose (homozygote) – one DNA dose from each parent – that the deadly Anemia shows up from birth.

   This has raised the possibility that gene therapy could cure SCA and pointed a direction for research. In fact bone marrow stem cell transplants of stem cells with the normal gene have cured some sickle cell disease.

   In Sickle Cell Anemia (SCA) a gene of the DNA produces a poorly functioning protein in place of normal protein and a double dose of the gene, one gene dose each from Mom and from Dad, is needed for full disease to develop.

   This is also an example of a recessive gene, meaning both Mother and Father must donate at least single dose of it in the offspring's chromosome pair involved in the disease and the afflicted child must have the double dose for it to do harm.

Cloning of Genes: Today, any gene can be cloned. How? First, a DNA sample is obtained (from mouth, blood or any tissue that contains enough cells to isolate DNA molecules). Then the DNA is can be heated to 95⁰ C (Other chemical techniques are now mostly used.) to separate the strands, and chemically treated to separate the genes, and the genes are identified by base pair sequences. Once the gene is identified and localized to a segment of DNA, it can be spliced out and inserted into the DNA of a virus or into bacteria and the germs can be grown in culture overnight to produce millions of themselves with billions of the gene copies. That is the process of cloning a gene that may be used in future gene therapies as it is in SCA. (Note: it is not exactly the same as the cloning of a living organism, which involves a more complex mechanism)

End of the Chapter. For next, click

3.7 The HLA System - Predictor of Disease