INTRODUCTION

The cells composing the body continue to divide throughout life. Cell division ensures sustenance and propagation of life. As the cells grow, they reproduce themselves, where a diploid cell splits to produce new diploids, each of which is a replica of the original. Without cell division, an organisms cells would not regenerate, resulting in not only cell death but also the death of the entire organism.

Cell division
Cell division is a process by which a cell called the parent cell, divides into two or more cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle.

PHASES OF CELL CYCLE

Interphase: G1, S and G2 Cell Division: M

Interphase
The cell prepares itself for cell division. Interphase is therefore not part of mitosis. In this, G1 (first gap), S (synthesis), and G2 (second gap). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only during the S phase. Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G2), and divides (M).

MITOSIS
Mitosis is the process in which a cell separates the chromosomes in its cell nucleus, into two identical sets. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two daughter cells. Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle.

FEATURES
It occurs only in somatic cells. It ensures sustenance of life. The cell. daughter cells carry same number of chromosomes as parent

PHASES
Mitosis

Prophase

Metaphase

Anaphase

Telophase

Prophase
At the beginning of the prophase, the chromosomes become contracted and thus much thicker and can be fixed and stained. While entering in prophase chromosomes have already split longitudinally into two chromatids, but they remain attached to each other at the centromere.

Metaphase
The nuclear membrane disappears and chromosomes become oriented in the centre of the nucleus. The spindle formation occurs at this time. This structure is responsible for the movement of chromosomes to the opposing poles of the cell. The centrosome divides into two and moves to the opposite poles of the nucleus and remains in connection with the spindle.

Anaphase
The onset of this phase is marked by division of centromere into two of each chromosome. This divided centromere then repels each other, so that the two chromatids are dragged apart in opposite direction towards the pole of the spindle.

Telophase
The daughter chromosomes (chromatids) have separated completely and the nuclear membrane now reappears enclosing the two groups of daughter chromosomes with cytoplasmic division over, the two new cells are formed and they enter into interphase.

Significance
The importance of mitosis is the maintenance of the chromosomal set; each cell formed receives chromosomes that are alike in composition and equal in number to the chromosomes of the parent cell. Transcription is generally believed to cease during mitosis, but epigenetic mechanisms such as bookmarking function during this stage of the cell cycle to ensure that the "memory" of which genes were active prior to entry into mitosis are transmitted to the daughter cells.

Consequences of errors
Although errors in mitosis are rare, the process may go wrong, especially during early cellular divisions in the zygote. Mitotic errors can be especially dangerous to the organism because future offspring from this parent cell will carry the same disorder.

 In non-disjunction, a chromosome may fail to separate during anaphase. One daughter cell will receive both sister chromosomes and the other will receive none. This results in the former cell having three chromosomes coding for the same thing a condition known as trisomy, and the latter cell having only one chromosome (the homologous chromosome), a condition known as monosomy.

 Mitosis is a traumatic process. The cell goes through dramatic changes in ultra structure, its organelles disintegrate Occasionally, chromosomes may become damaged. An arm of the chromosome may be broken and the fragment lost, causing deletion. The fragment may incorrectly reattach to another, non-homologous chromosome, causing translocation.

It may reattach to the original chromosome, but in reverse orientation, causing inversion. It may be treated erroneously as a separate chromosome, causing chromosomal duplication.

MEIOSIS
Meiosis is a process of reductional division in which the number of chromosomes per cell is cut in half. In animals, meiosis always results in the formation of gametes, while in other organisms it can give rise to spores.

FEATURES
It occurs only in germ cells. It is a reduction division (chromosomes halved from 46 to 23). It includes two successive divisions (Meiosis 1 and Meiosis 2). Meiosis determines inheritance ensures propagation of species. and

PROCESS
Meiosis is the process of nuclear division, which occurs when the gametes are formed. Meiosis takes place in two steps, each of which has a prophase, metaphase, anaphase and telophase stages as in mitosis. The preparatory steps that lead up to meiosis are identical in pattern and name to the interphase of the mitotic cell cycle. Interphase is followed by meiosis 1 and then meiosis 2.

Interphase
Gap 1(G1) : This is a very active period, where the cell synthesizes its vast array of proteins, including the enzymes and structural proteins it will need for growth. In G1 stage, each of the chromosomes consists of a single (very long) molecule of DNA. In humans, at this point cells are 46 chromosomes, 2N, identical to somatic cells.

 Synthesis (S) phase: The genetic material is replicated: duplicates, each of its producing 46 chromosomes chromosomes

each made up of two sister chromatids. The cell is still considered diploid because it still contains the same number of centromeres. Gap 2 (G2) phase: G2 phase is absent in Meiosis

Meiosis-phase
In meiosis I, the homologous pairs in a diploid cell separate, producing two haploid cells (23 chromosomes, N in humans), so meiosis I is referred to as a reductional division. A regular diploid human cell contains 46 chromosomes and is considered 2N because it contains 23 pairs of homologous chromosomes. In meiosis II, an equational division similar to mitosis will occur whereby the sister chromatids are finally split, creating a total of 4 haploid cells (23 chromosomes, N) per daughter cell from the first division.

Prophase I
Homologous chromosomes pair (or synapse) and crossing over (or recombination) occurs - a step unique to meiosis. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatids, with one chromosome coming from each parent.

 Leptotene :The first stage of prophase I is the leptotene stage, also known as leptonema, from Greek words meaning "thin threads. During this stage, individual chromosomes begin to condense into long strands within the nucleus. Zygotene : The zygotene stage, also known as zygonema, from Greek words meaning "paired threads,"occurs as the chromosomes approximately line up with each other into homologous chromosomes.

Diplotene
During the diplotene stage, also known as diplonema, from Greek words meaning "two threads, the homologous chromosomes separate from one another a little. The chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the homologous chromosomes of each bivalent remain tightly bound, the regions where crossing-over occurred.

Diakinesis
Chromosomes condense further during the diakinesis stage, from Greek words meaning, "Moving through." This is the first point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly visible. Other than this observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli disappear, the nuclear membrane disintegrates into vesicles, and the meiotic spindle begins to form.

Synchronous processes
During these stages, two centrosomes, containing a pair of centrioles in animal cells, migrate to the two poles of the cell. These centrosomes, which were duplicated during S-phase, function as microtubule organizing centers nucleating microtubules, which are essentially cellular ropes and poles. The microtubules invade the nuclear region after the nuclear envelope disintegrates, attaching to the chromosomes a the kinetochore. The kinetochore functions as a motor, pulling the chromosome along the attached microtubule toward the originating centriole, like a train on a track. There are four kinetochores on each tetrad, but the pair of kinetochores on each sister chromatid fuses and functions as a unit during meiosis I.

Metaphase I
Homologous pairs move together along the metaphase plate: As kinetochore microtubules from both centrioles attach to their respective kinetochores, the homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores of homologous chromosomes.

Anaphase I
Kinetochore microtubules shorten, severing the recombination nodules and pulling homologous chromosomes apart. Since each chromosome has only one functional unit of a pair of kinetochores, whole chromosomes are pulled toward opposing poles, forming two haploid sets. Each chromosome still contains a pair of sister chromatids. Nonkinetochore microtubules lengthen, pushing the centrioles farther apart. The cell elongates in preparation for division down the center.

Telophase I
The last meiotic division effectively ends when the chromosomes arrive at the poles. Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair of chromatids. The microtubules that make up the spindle network disappear, and a new nuclear membrane surrounds each haploid set. The chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant cells, occurs, completing the creation of two daughter cells. Sister chromatids remain attached during telophase I.

Meiosis II
Meiosis II is the second part of the meiotic process. Much of the process is similar to mitosis. The end result is production of four haploid cells (23 chromosomes, 1N in humans) from the two haploid cells (23 chromosomes, 1N * each of the chromosomes consisting of two sister chromatids) produced in meiosis I.

 Prophase II takes an inversely proportional time compared to telophase I. In this prophase we see the disappearance of the nucleoli and the nuclear envelop again as well as the shortening and thickening of the chromatids. Centrioles move to the polar regions and arrange spindle fibers for the second meiotic division. In metaphase II, the centromeres contain two kinetochores, that attach to spindle fibers from the centrosomes (centrioles) at each pole. The new equatorial metaphase plate is rotated by 90 degrees when compared to meiosis I, perpendicular to the previous plate.

 This is followed by anaphase II, where the centromeres are cleaved, allowing microtubules attached to the kinetochores to pull the sister chromatids apart. The sister chromatids by convention are now called sister chromosomes as they move toward opposing poles. The process ends with telophase II, which is similar to telophase I, and is marked by uncoiling and lengthening of the chromosomes and the disappearance of the spindle. Nuclear envelopes reform and cleavage or cell wall formation eventually produces a total of four daughter cells, each with a haploid set of chromosomes. Meiosis is now complete.

Significance of Meiosis
Meiosis facilitates stable sexual reproduction. Without the halving of ploidy, or chromosome count, fertilization would result in zygotes that have twice the number of chromosomes as the zygotes from the previous generation. Plants, however, regularly produce fertile, viable polyploids. Polyploidy has been implicated as an important mechanism in plant speciation. Most importantly, recombination and independent assortment of homologous chromosomes allow for a greater diversity of genotypes in the population. This produces genetic variation in gametes that promote genetic and phenotypic variation in a population of offspring.

Introduction
The law of inheritance were derived by Gregore Mendel, a 19th century Monk conducting hybridization experiments in garden peas. From these experiments he deducted two generalizations which later became known as Mendles laws of heredity or Mendelian Inheritance.

Cont.
Mendelian inheritance (or Mendelian genetics or Mendelism) is a set of primary tenets relating to the transmission of hereditary characteristics from parent organisms to their children; it underlies much of genetics. They were initially derived from the work of Gregor Mendel published in 1865 and 1866 which was "re-discovered" in 1900.

Mendel's Laws
The principles of heredity were written by Gregor Mendel in 1865. Mendel discovered that by crossing white flower and purple flower plants, the result was a hybrid offspring. He then conceived the idea of heredity units, which he called "factors", factors, later called genes, one which is a recessive characteristic and the other dominant.The dominant gene, such as the purple flower in Mendel's plants, will hide the recessive gene, the white flower. After Mendel self-fertilized the F1 generation and obtained the 3:1 ratio, he correctly theorized that genes can be paired in three different ways for each trait; AA, aa, and Aa. The capital A represents the dominant factor and lowercases a represent the recessive.

Cont
Mendel stated that each individual has two factors for each trait, one from each parent. The two factors may or may not contain the same information. If the two factors are identical the individual is called homozygous for the trait. If the two factors have different information, the individual is called heterozygous. The alternative forms of a factor are called alleles. The genotype of an individual is made up of the many alleles it possesses. An individual's physical appearance, or phenotype, is determined by its alleles as well as by its environment.

Cont
An individual possesses two alleles for each trait; one allele is given by the female parent and the other by the male parent. They are passed on when an individual matures and produces gametes, egg and sperm. When gametes form the paired alleles separate randomly so that each gamete receives a copy of one of the two alleles. The presence of an allele doesn't promise that the trait will be expressed in the individual that possesses it. In heterozygous individuals the only allele that in expressed is the dominant. The recessive allele is present but its expression is hidden.

Mendels Findings
Law of Segregation
The Law of Segregation states that when any individual produces gametes, the copies of a gene separate, so that each gamete receives only one copy. A gamete will receive one allele or the other. In meiosis the paternal and maternal chromosomes get separated and the alleles with the characters are segregated into two different gametes.

Law of Independent Assortment

The Law of Independent Assortment, also known as "Inheritance Law", states that alleles of different genes assort independently of one another during gamete formation. Mendel's experiments with mixing one trait always resulted in a 3:1 ratio between dominant and recessive phenotypes, his experiments with mixing two traits showed 9:3:3:1 ratios.

 The 9:3:3:1shows that each of the two genes are independently inherited with a 3:1 ratio. Mendel concluded that different traits are inherited independently of each other, so that there is no relation, for example, between a cat's color and tail length. This is actually only true for genes that are not linked to each other.

Cont
Independent assortment occurs during meiosis I in eukaryotic organisms, specifically anaphase I of meiosis, to produce a gamete with a mixture of the organism's maternal and paternal chromosomes. The 46 chromosomes in a normal diploid human cell, half are maternally-derived and half are paternally-derived. During gametogenesis - the production of new gametes by an adult - the normal complement of 46 chromosomes needs to be halved to 23 to ensure that the resulting haploid gamete can join with another gamete to produce a diploid organism.

INTRODUCTION
The idea of mutation first originated from observations of a Hugo de Vries(1880s) on variations in plants. He found that heritable variations were distinct from environmental variations. He gave the name mutation to heritable changes. In 1901 published a book entitled The Mutation Theory. Although De Vries is credited with the discovery of the idea of mutations.

MUTATION
A mutation occurs when a DNA gene is damaged or changed in such a way as to alter the genetic message carried by that gene. A mutation is a permanent change in the DNA sequence of a gene. Mutation is a genes DNA sequence can alter the amino acid sequence of the protein encoded by the gene. Like words in sentence, the DNA sequence of each gene determines the amino acid sequence for the protein it encodes. The DNA sequence is interpreted in groups of three nucleotide bases, called condos. Each Condon specifies a single amino acid in a protein.

The DNA sequence of a gene as a sentence made up entirely of three letter words. In the sentence, each three letter word is a Condon, specifying a single amino acid in a protein. Eg: Thesunwashotbuttheoldmandidnotgetthishot. If you were split this sentence into there letter words, it becomes * The sun was hot but the old man did not get this hot. If you shifted the three letter reading frame, it becomes * T hes unw ash otb uttbheo ldm and idn olg eth ish at. * Th esu sho tbu tth eol dma ndi dno tge this ha t. As only one of these three reading frames translate into understandable sentence. In the same way, only one three letter reading frame within a gene codes for the correct protein. OR

 The early concepts of mutation therefore arose out of genetic studies of visible phenotypes. Later by the middle of the twentieth century, the molecular basis of heredity began to be investigated. It became established that the transmission of hereditary traits takes place due to an accurate process of self replication of the genetic material DNA.

WAYS OF MUTATION
INHERITED: Mutations that are passed from parent to child are called hereditary or germline mutation. This type of mutation is present throughout a persons life in virtually every cell in the body. ACQUIRED: Mutation occur in the DNA of individual cells at some time during a persons life. These changes can be caused by environment factors such as ultraviolet radiation from the sun or can occur if a mistake is made as DNA copies itself during cell division. These mutations can be passed on to the next generation.

TYPES OF MUTATIONS
Single base substitutions Insertions and deletions Chromosomal mutations

Single base substitutions

A single nucleotide base is replaced. These single base changes are also called point mutations. If a purine (a, t) replaces a purine or a pyrimidine (c, g) replaces a pyrimidine, it is called a transition. If a purine replaces a pyrimidine or vice-versa, the substitution is called a transversion.

1. Missense mutations
In a missense mutation, the new base alters a condon resulting in a different amino acid being incorporated into the protein chain. This is what happens in sickle cell anaemia. The 17th nucleotide of the gene for the beta chain of haemoglobin is changed from an 'a' to a 't'. This changes the codon from 'gag' to 'ggt' resulting in the 6th amino acid of the chain being changed from glutamic acid to valine. This apparently trivial alteration to the beta globin gene alters the quaternary structure of haemoglobin, which has a profound influence on the physiology and wellbeing of the individual.

2. Nonsense mutations In a nonsense mutation, the new base changes a codon that specified an amino acid into one of the stop codons (taa, tag, tga). This will cause translation of the mRNA to stop prematurely and a truncated protein to be produced. This truncated protein will be unlikely to function correctly. Nonsense mutations occur in between 15% to 30% of all inherited diseases including cystic fibrosis, haemophilia, retinitis.

3. Silent mutations

Silent mutations are those that cause no change in the final protein product and can only be detected by sequencing the gene. Most amino acids that make up a protein are encoded by several different codons. So, if for example, the third base in the 'cag' codon is changed to an 'a' to give 'caa', a glutamine (Q) would still be incorporated into the protein product, because the mutated codon still codes for the same amino acid. These types of mutations are 'silent' and have no detrimental effect.

Insertion and Deletion

Extra base pairs may be added or deleted from the DNA of a gene. The number of bases can range from a few to thousands. Insertions and deletions of one or two bases or multiples of one or two cause frameshifts (shift the reading frame). These can have devastating effects because the mRNA is translated in new groups of three nucleotides and the protein being produced may be useless.

Chromosomal Mutation
A chromosome mutation is any change in the structure or arrangement of the chromosomes. Mutations to chromosomes happen most frequently meiosis. There are many different types of mutation that can change the chromosome structure resulting in changes to the genotype and phenotype of the organism. Chromosomal mutations effecting essential parts of the DNA can result in the abortion of the fetus before birth.

Translocations

y Translocations are the transfer of a piece of one chromosome to a non-homologous chromosome. They are often reciprocal, with the two chromosomes swapping segments with each other. An abnormal hybrid gene is created leading to the production of a novel protein that is not normally found in the cell. This protein prevents normal growth and development, leading to leukaemia.

 Deletions - A large section of a chromosome can be deleted resulting in the loss of a number of genes.

Duplications

In

this

mutation, some genes are duplicated and displayed twice on the same chromosome.

y Chromosome non-disjunction - During

cell division, the chromosomes fail to successfully separate to opposite poles, resulting in one of the daughter cells having an extra chromosome and the other daughter cell lacking one. y If this non-disjunction occurs in chromosome 21 of a human egg cell, a condition called Downs syndrome (DS) occurs. A person suffering with DS has 47 chromosomes in every cell instead of the normal 46.

Causes of Mutations
DNA fails to copy accurately Most of the mutations that we think matter to evolution are "naturallyoccurring." For example, when a cell divides, it makes a copy of its DNA and sometimes the copy is not quite perfect. That small difference from the original DNA sequence is a mutation.

External influences can create mutations

Mutations can also be caused by exposure to specific chemicals or radiation. These agents cause the DNA to break down. Nevertheless, when the cell repairs the DNA, it might not do a perfect job of the repair. So the cell would end up with DNA slightly different than the original DNA and hence, a mutation.

INTRODUCTION
The human genome project was an international research effort to determine the sequence of the human genome and identify the genes that it contains. The project was coordinated by the national institutes of health and the US department of energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, China and India. The human genome project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule.

Cont
The work of the human genome project has allowed researchers to begin to understand the blueprint for building a person. As researcher learn about more the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology and the life sciences. The Human Genome Project, one of the most significant research of the twentieth century deserves much of the credit for the discovery of these new applications of genetic information. Especially research from the HGP is providing a new and better understanding of the genetic contribution to disease, the development of targeted drug therapy and the development of genetic tests that identify those who may have or are at risk for genetic disease.

GOALS OF HGP
The main goals of the human genome project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. In addition to sequencing DNA, the human genome project sought to develop new tools to obtain and analyze the data and to make this information widely available. The human genome project committed to exploring the consequences of genomic research through its ethical, legal, and social implications (ELSI) program.

ACCOMPLISHMENTS OF HGP
In April 2003, researchers announced that the human genome project had completed a highquality sequence of essentially the entire human genome. This sequence closed the gaps from a working draft of the genome, which has published in 2001. It also identified the locations of many human genes and provided information about their structure and organization. The project made the sequence of the human genome and tools to analyze the data freely available via the internet.

Cont
In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including yeast, the roundworm, and the fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life.

ETHICAL, LEGAL AND SOCIAL IMPLICATIONS OF HGP

The ethical, legal and social implications (ELSI) program was founded in 1990 as an integral part of the Human Genome Project. The mission of the ELSI program was to identify and address issues raised by genomic research that would affect individuals, families, and society. A percentage of the Human Genome Project budget at the National Institute of Health and the US Department of Energy was devoted to ELSI research.

The ELSI program focused on the possible consequences of genomic research in four main areas
Privacy and fairness in the use of genetic information, including the potential for genetic discrimination in employment and insurance. The integration of new genetic technologies, such as genetic testing, into the practice of clinical medicine. Ethical issues surrounding the design and conduct of genetic research with people, including the process of informed consent. The education of healthcare professionals, policy makers, students and the public about genetics and the complex issues that result from genomic research.

FUTURE PRESPECTIVE OF GENOMIC RESEARCH

Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being. The next stage of genomic research will begin to drive meaningful knowledge from the DNA sequence research studies that build on the work of the human genome project are under way worldwide.

Objectives of Continued Genomic Research

Determine the function of genes and the elements that regulate genes throughout the genome. Find variations in the DNA sequence among people and determine their significance. These variations may one day provide information about persons disease risk and response to certain medications. Discover the 3 dimensional structures of proteins and identify their functions. Explore how DNA and proteins interact with one another and with the environment to create complex living systems.

Cont
Develop and apply genome based strategies for the early detections, diagnosis and treatment of disease. Sequence the genomes of other organisms, such as the rat, cow and chimpanzee, in order to compare similar genes between species. Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently. Continue to explore the ethical, legal and social issues raised by genomic research.

Finally, human genome project research will help solve one of the greatest mysteries of life how does one fertilized egg know to give rise to so many different specialized cells, such as those making up muscles, brain, heart, eyes skin, blood and so on? For a human being or any organism to develop normally, a specific gene or set of genes must be switched on the right place in the body at exactly the right movement in development. Information generated by the human genome project will shed light on how this intimate dance of gene activity is choreographed into the wide variety of organs and tissues that make up a human being.

Introduction
The series has focused on the ways in which the rapidly appearing tools of genomics have already begun to change the practice of medicine. In this issue, Burke explores how genomics has started to improve our understanding of the biology of health and disease in ways that was never before possible. Although the series demonstrates that genomics has indeed begun to change the practice of medicine, it catalogues only the birth of the genomic era and thus no more captures in detail the ultimate effect of genomic medicine.

Origin
If the genomic era can be said to have a precise birth date, it was in the midst of the appearance of the series, on April 14, 2003. That was when the international effort known as the Human Genome Project put a close to the pregenomic era with its announcement that it had achieved the last of the project's original goals, the complete sequencing of the human genome. The extent and pace of progress in genomics are suggested by the fact that this achievement occurred 11 days shy of the 50th anniversary of the publication of Watson and Crick's seminal description of the DNA double helix.

 If science, technology, and medicine have consistently demonstrated anything, it is that they proceed at an ever-quickening pace. That we have gone in the past 50 years from the first description of the structure of our DNA to its complete sequencing gives some indication of how much the impact of genomic medicine on the health care of today's neonates will increase by the time they turn 50 years of age.

 However, it is not solely the next 50 years that will witness important advances in genomic medicine. Many such advances have already occurred, including some during the interval since the launch of the Genomic Medicine series.

Uses
The use of genomics for the rapid identification of newly discovered pathogens such as that involved in the severe acute respiratory syndrome (SARS), the use of gene-expression profiling to assess prognosis and guide therapy, as in breast cancer. The use of genotyping to stratify patients according to the risk of a disease, such as the long-QT syndrome or myocardial infarction, the use of genotyping to shed light on the response to certain drugs, such as antiepileptic agents. The use of genomic approaches in the design and implementation of new drug therapies, and to improve our understanding of the role of specific genes in the causation of common conditions, such as obesity.

 During this same brief period, other notable genomics-based advances in our understanding of biology and of health have included the first comprehensive analysis of human chromosome 7, clarification of the malespecific region of the human Y chromosome, and the identification of the gene responsibility.

 In recent months we have seen not only the promise of the genomic era with respect to medicine, but also its pitfalls. An example of the latter has been the revelation that confusion and misinformation have occasionally accompanied the counseling of persons who undergo screening for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) the gene responsible for cystic fibrosis.

 Genomics provides powerful means of discovering hereditary factors in disease. But even in the genomic era, it is not genes alone but the interplay of genetic and environmental factors that determines phenotype (i.e., health or disease). This point is not new, but it bears repeating. For example, a mutation in CHE1 may be innocuous until a person carrying it is exposed to succinylcholine chloride anesthesia, when it leads to prolonged apnea

 Recent reports further expand our knowledge of the complex interactions between genes and the environment. For instance, one such study suggests that common variations in the serotonintransporter gene influence the likelihood of depression after exposure to stress. Since it remains difficult to alter genes in human for the next couple of decades we will generally use personalized modifications of the environment, and not of genes, to translate genomics-based knowledge into improvements in health for most of our patients.

 With the end of the pregenomic era in sight, more than 600 experts recently collaborated to produce a vision for the future of genomic research and its applications to biology, health, and society. According to that vision, within a decade or two, it will be possible to sequence anyone's entire genome for a laboratory cost of less than $1,000. If this proves true, one can imagine how not only research, but also clinical care, may change dramatically.

With particular relevance in the United States, is the understandable concern of many patients that obtaining genetic information important to their health care is not worth the risk of discrimination stemming from the use of such information by potential insurers or employers. Although more than 40 states limit employers' and insurers' access to or use of genetic information, many people believe that only the passage of legislation mandating uniform national protection against the misuse of such information will lead to full use of genetic testing. Congressional leaders from both major parties and the current administration have supported such federal legislation, and passage of such legislation is currently closer to reality than ever before. However, until it is enacted and signed into law, the fear of discrimination will remain.

 Other social issues require our attention if genomic medicine is to benefit our patients. How should genetic tests be regulated? What, if any, are the appropriate uses of direct-to-consumer marketing of genetic tests? The Internet has recently had a proliferation of genetic-testing sites that feature claims grounded in greed and pseudoscience, rather than in data or reality. How will health care providers and the public distinguish between these and responsible testing services, whether they are available through the Internet or in the hospital?

 It would be easy to assume that for the foreseeable future the benefits of genomic medicine will accrue only to people in developed countries. However, even in resource-poor regions of the world, genomic approaches can offer dramatic benefits to health, as the publication within the past year of the genomes for Plasmodium falciparu.

 While recognizing such challenges, we look forward with curiosity and real hope to the advances of the next 50 years the first 50 years of the genomic era. As evidenced by the Genomic Medicine series, today's researchers and clinicians have already started to use the power of genomics to improve health, and we anticipate that this is but a hint of the progress to come.