Genetics

Uses of Genetic Study

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Diagnostic testing
Diagnostic testing is used to identify or confirm the diagnosis of a disease or condition in a person or a family. Diagnostic testing gives a "yes" or "no" answer in most cases. It is sometimes helpful in determining the course of a disease and the choice of treatment. Examples of diagnostic testing include chromosome studies, direct DNA studies, and biochemical genetic testing.

Predictive genetic testing
Predictive genetic testing determines the chances that a healthy individual with or without a family history of a certain disease might develop that disease. There is predictive testing available for some adult-onset conditions (those diseases which manifest themselves in adulthood) such as some types of cancer, cardiovascular disease, and some single gene disorders.

Presymptomatic genetic testing
Presymptomatic genetic testing is used to determine whether persons who have a family history of a disease, but no current symptoms, have the gene alterations associated with the disease.

Carrier testing
Carrier testing is performed to determine whether a person carries one copy of an altered gene for a particular disease. The disease may be autosomal recessive, which means that the disease is present in an individual only if two copies of the altered gene are inherited. Couples who both carry the same autosomal recessive gene have a one in four, or 25 percent, chance with each pregnancy to have a child with that disease.

A recessive disease may also be X-linked recessive, which means that the altered gene is located on the X chromosome. Since females have two X chromosomes, and males have one X and one Y chromosome, females can be carriers of a gene on the X but are not affected (provided the other X has the normal copy of the gene). On the other hand, males are usually affected with the disease, if they have the altered gene on their X chromosome (because they do not possess the normal copy of the gene on the Y chromosome). Therefore, "carrier testing" for X-linked conditions is usually done in females.

Prenatal diagnosis
Prenatal diagnosis is used to diagnose a genetic disease or condition in the developing fetus and includes maternal serum screening, ultrasound (sonograms), amniocentesis, chorionic villus sampling (CVS), and percutaneous umbilical blood sampling (PUBS).

Preimplantation studies
Preimplantation studies are used following in vitro fertilization to diagnose a genetic disease or condition in an embryo before it is implanted into the mother's uterus.

Newborn screening
Newborn screening is performed in newborns in state public health programs to detect certain genetic diseases for which early diagnosis and treatment are available.

COMPLETE DETAILS OF D.N.A

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GROOVES IN D.N.A

Grooves in DNA

Twin helical strands form the DNA backbone. Another double helix may be found by tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide.[14] The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove.[15] This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

BASE PAIRING

In a DNA double helix, each type of nucleobase on one strand normally interacts with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature.[16] As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

Most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart – a process known as melting – to form two ss DNA molecules. Melting occurs when conditions favor ssDNA; such conditions are high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

Base Pairing in DNA

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.

In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.

　

SENSE AND ANTISENSE

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[20] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.[21] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

SUPERCOILING

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.

Relaxed and Supercoiled DNA

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns— and also B-DNA used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James D. Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.

Although the `B-DNA form' is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.

ALTERNATIVE DNA CHEMESTRY

For a number of years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA.

A December 2010 NASA press conference stated that the bacterium GFAJ-1, which has evolved in an arsenic-rich environment, is the first terrestrial lifeform found which may have this ability. The bacterium was found in Mono Lake, east of Yosemite National Park. GFAJ-1 is a rod-shaped extremophile bacterium in the family Halomonadaceae that, when starved of phosphorus, may be capable of incorporating the usually poisonous element arsenic in its DNA. This discovery may lend weight to the long-standing idea that extraterrestrial life could have a different chemical makeup from life on Earth. The research was carried out by a team led by Felisa Wolfe-Simon, a geomicrobiologist and geobiochemist, a Postdoctoral Fellow of the NASA Astrobiology Institute with Arizona State University. This finding has, however, faced strong criticism from the scientific community; scientists have argued that there is no evidence that arsenic is actually incorporated into biomolecules.[42][43] Independent confirmation of this finding has also not yet been possible.

　

QUADRUPLEX STRUCTURE

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3' ends of chromosomes.These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected.In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.
　
　

　

DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.

　

　

BRANCHED DNA

In DNA fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

　

Branched B-DNA

Vibration

DNA may carry out low-frequency collective motion as observed by the Raman spectroscopy and analyzed with a quasi-continuum model.

Chemical modifications

Base modification

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. For example, cytosine methylation, produces 5-methylcytosine, which is important for X-chromosome inactivation. The average level of methylation varies between organisms – the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,and the glycosylation of uracil to produce the "J-base" in kinetoplastids.

Damage

A covalent adduct between a metabolically activated form of benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage.[65] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations.These mutations can cause cancer. Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. In order for an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts which induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.

The Technical Term "Genetics"

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Genetics (from Antient Greek: γενετικός genetikos, "genitive" and that from γένεσις genesis, "origin"), a discipline of biology, is the science of genes, heredity and variations in living organisms.

Genetics deals with the molecular structure and functions of genes, gene behavior in context of a cell or organism (e.g. dominance and epigenetics), patterns of inheritance from parent to offspring, and gene distribution, variation and change in populations such as through Genome-Wide Association Studies. Given that genes are universal to living organisms, genetics can be applied to the study of all living systems, from virus and bacteria, through plants and domestic animals to humans (as in medical genetics).

The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-19th century. Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits via discrete units of inheritance, which are now called genes.

Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides—the sequence of these nucleotides is the genetic information organisms inherit. DNA naturally occurs in a double stranded form, with nucleotides on each strand complementary to each other. Each strand can act as a template for creating a new partner strand. This is the physical method for making copies of genes that can be inherited.

The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids creating proteins the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship between nucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a protein's amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole.

Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining an organism's size, nutrition and health it experiences after inception also have a large effect.

Basic Concepts Of Genetics

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Have you ever wondered why an elephant always gives birth only to a baby elephant and not some other animal? Or why a mango seed forms only a mango plant and not other plants?

Given that they do, are the offspring identical to their parents? Or do they show differences in some of their characteristics? Have you ever wondered why siblings sometimes look so similar to each other? Or sometimes even so different?

These and several related questions are dealt with, scientifically, in a branch of biology known as Genetics. This subject deals with the inheritance, as well as the variation of character from parents to off springs Inheritance is the process by which character are passed on from parent to progeny; it is the basis of heredity. Variation is the degree by which progeny differ from their parents.

Human knew from early as 8000-1000 B.C. that one of the cause of variation was hidden in sexual reproduction, They exploited the variation that were naturally present in the wild population of plants and animals to selectively breeds and select of organism that possessed desirable characters. For example, through artificial selection and domestication from ancestral wild cows, we have well-known German breed Cows and India Breeds etc.We must, however, recognize that though our ancestors knew about the inheritance of character and variation, they had very little idea about the scientific basis of these phenomena.

MENDEL’S LAWS OF INHERITANCE

7 Contrasting Characters Of Pea

It was during mid nineteenth century that headway was made in the understanding of inheritance. Gregor Mendel, conduct hybridization experiment on garden peas for seven years (1856-1863) and proposed the law of inheritance in living organism. During Mendel’s investigation into inheritance patterns it was for the first time that statistical analysis and mathematical logic were applied to problems in biology. His experiment has a large sampling size, which gave greater credibility to the data that he collected. Also, l the confirmation of his inferences from experiment on successive generation of his test plants proved that his result pointed to general rule of ideas. Inheritance rather than being unsubstantiated

Mendel conducted such artificial pollination/cross pollination experiment using several true breeding pea lines. A true breeding line is one that, having undergone continuous self pollination, shows the stable trait inheritance and expression for several generations. Mendel selected 14 true breeding pea plant varieties as pair which are similar except for one character with contrasting trait. Some of the contrasting trait selected were smooth or wrinkled seeds, yellow or green seeds, smooth or inflated pods, green or yellow pods, and tall or dwarf plants.

INHERITANCE OF ONE GENE

Let us take example of one such hybridization experiment carried out by Mendel where he crossed tall and dwarf pea plants to study the inheritance of one gene .he collected the seeds to produce as a result of this cross and grew them to generate plants of the first hybrid generation. This generation is also called as first filial progeny or the F1.Mendel observed that all the f1 progeny plant were tall, like one of its parents; none where dwarf. He made similar observation for the other pair of trait-he found that the f1 always resemble either on e of the parents and that the trait of the other parent was not seen in them.

Checkerboard diagram of Di Hybrid Cross

Mendel then self pollination the tall F1 plants and to his surprised found that in the filial second generation some of the off spring were dwarf the character that was not seen in the f1 generation was now expressed. Then progeny of f1 filial plant that were dwarf were ¼ of the F2 plant while ¾ of the F2 plant were tall. The tall and dwarf trait were identical to their parental type did not show any blending, that is all the offspring were either tall or dwarf, none were of in between height.

Similar result were obtained with the other trait that he studied: only one of the parental trait was expressed in the F1 generation while at the F2 stage both the trait were expressed in the proportion 3:1. The contrasting trait did not show any blending at either F1 or F2 stage.

Di Hybrid Cross

Based on these observations, Mendel proposed that something was being stably passed down, unchanged, from parents to offsprings through the gametes, over successive generations. He called these things as “factors”. Now we call them as genes. Genes, therefore, are the units of inheritance. They contain the information that is required to express a particular trait in an organism. Genes which code for a pair of contrasting traits are known as alleles, i.e: they are slightly different forms of the same gene. If we use alphabetical symbols for each genes, then the capital letter is used for the traits expressed at the F1 stage and the small alphabet for the other trait. For example, in case of the character of height, T is used for the Tall trait and the t for the Dwarf and T and t are alleles of each other, Hence, in plants the pair of alleles for height would be TT,Tt or tt. Mendel also proposed that in a true breeding, tall or dwarf pea variety the allelic pair of genes for height are identical or homozygous, TT and tt respectively. TT and tt are called the genotype of the plant while the driscriptive terms tall and dwarf are the phenotypes. What then would be the phenotype of a plant that had a genotype Tt?

Mono Hybrid Cross

As Mendel found the phenotype of the F1 hetrozygote—Tt exactly like the TT parent in appearance, he proposed that in a pair of dissimilar factors, one Dominant the other(as in the F1) and hence is called the Dominant Factor while the other is recessive. In this case T(for tallness) is dominant over t(for dwarfness), that is recessive. He observed identical behavior for all the other characters/ traits pairs that he studied. It is convenient( and logical) to use the capital and lower case of an alphabetical symbol to remember this concept of Dominance and Recessiveness. (Do not use capital T for tall and d for dwarf because you will find it difficult to remember weather T and d are alleles of the same genes/characters or not). Alleles can be similar as in the case of homozygotes TT and tt or can be dissimilar as in the case of hetrozygote—Tt. Since the Tt plant is heterozygous for genes controlling one character(height), it is a mono hybrid and the cross between TT and tt is a monohybrid cross.