Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis and counselling people with genetic disorders would be considered part of medical genetics. In contrast, the study of non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not relevant to medical genetics. Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, the emerging new medical specialty, predictive medicine. Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, nutritionists, clinical diagnostic laboratory activities, research into the causes and inheritance of genetic disorders.
Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology, mental retardation, mitochondrial disorders, skeletal dysplasia, connective tissue disorders, cancer genetics and prenatal diagnosis. Medical genetics is becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics are revealing etiologies for neurologic, cardiovascular, ophthalmologic, renal and dermatologic conditions; the medical genetics community is involved with individuals who have undertaken elective genetic and genomic testing. In some ways, many of the individual fields within medical genetics are hybrids between clinical care and research; this is due in part to recent advances in science and technology that have enabled an unprecedented understanding of genetic disorders. Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders. Referrals are made to genetics clinics for a variety of reasons, including birth defects, developmental delay, epilepsy, short stature, many others.
Examples of genetic syndromes that are seen in the genetics clinic include chromosomal rearrangements, Down syndrome, DiGeorge syndrome, Fragile X syndrome, Marfan syndrome, Neurofibromatosis, Turner syndrome, Williams syndrome. In the United States, Doctors who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics. In order to become a board-certified practitioner of Clinical Genetics, a physician must complete a minimum of 24 months of training in a program accredited by the ABMGG. Individuals seeking acceptance into clinical genetics training programs must hold an M. D. or D. O. degree and have completed a minimum of 24 months of training in an ACGME-accredited residency program in internal medicine, pediatrics and gynecology, or other medical specialty. Metabolic genetics involves the diagnosis and management of inborn errors of metabolism in which patients have enzymatic deficiencies that perturb biochemical pathways involved in metabolism of carbohydrates, amino acids, lipids.
Examples of metabolic disorders include galactosemia, glycogen storage disease, lysosomal storage disorders, metabolic acidosis, peroxisomal disorders and urea cycle disorders. Cytogenetics is the study of chromosomes and chromosome abnormalities. While cytogenetics relied on microscopy to analyze chromosomes, new molecular technologies such as array comparative genomic hybridization are now becoming used. Examples of chromosome abnormalities include aneuploidy, chromosomal rearrangements, genomic deletion/duplication disorders. Molecular genetics involves the discovery of and laboratory testing for DNA mutations that underlie many single gene disorders. Examples of single gene disorders include achondroplasia, cystic fibrosis, Duchenne muscular dystrophy, hereditary breast cancer, Huntington disease, Marfan syndrome, Noonan syndrome, Rett syndrome. Molecular tests are used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman syndrome, Beckwith-Wiedemann syndrome, Prader-willi syndrome, uniparental disomy.
Mitochondrial genetics concerns the diagnosis and management of mitochondrial disorders, which have a molecular basis but result in biochemical abnormalities due to deficient energy production. There exists some overlap between molecular pathology. Genetic counseling is the process of providing information about genetic conditions, diagnostic testing, risks in other family members, within the framework of nondirective counseling. Genetic counselors are non-physician members of the medical genetics team who specialize in family risk assessment and counseling of patients regarding genetic disorders; the precise role of the genetic counselor varies somewhat depending on the disorder. Although genetics has its roots back in the 19th century with the work of the Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later, it started to develop, albeit during the first half of the 20th century. Mendelian inheritance was studied in a number of important disorders such as albinism and hemophilia.
Mathematical approaches were devised
Chondrogenesis is the process by which cartilage is developed. In embryogenesis, the skeletal system is derived from the mesoderm germ layer. Chondrification is the process by which cartilage is formed from condensed mesenchyme tissue, which differentiates into chondrocytes and begins secreting the molecules that form the extracellular matrix. Early in fetal development, the greater part of the skeleton is cartilaginous; this temporary cartilage is replaced by bone, a process that ends at puberty. In contrast, the cartilage in the joints remains unossified during the whole of life and is, permanent. Adult hyaline articular cartilage is progressively mineralized at the junction between cartilage and bone, it is termed articular calcified cartilage. A mineralization front advances through the base of the hyaline articular cartilage at a rate dependent on cartilage load and shear stress. Intermittent variations in the rate of advance and mineral deposition density of the mineralizing front, lead to multiple "tidemarks" in the articular calcified cartilage.
Adult articular calcified cartilage is penetrated by vascular buds, new bone produced in the vascular space in a process similar to endochondral ossification at the physis. A cement line demarcates articular calcified cartilage from subchondral bones. Once damaged, cartilage has limited repair capabilities; because chondrocytes are bound in lacunae, they cannot migrate to damaged areas. Because hyaline cartilage does not have a blood supply, the deposition of new matrix is slow. Damaged hyaline cartilage is replaced by fibrocartilage scar tissue. Over the last years and scientists have elaborated a series of cartilage repair procedures that help to postpone the need for joint replacement. In a 1994 trial, Swedish doctors repaired damaged knee joints by implanting cells cultured from the patient's own cartilage. In 1999 US chemists created an artificial liquid cartilage for use in repairing torn tissue; the cartilage is injected into a wound or damaged joint and will harden with exposure to ultraviolet light.
Researchers say their lubricating layers of "molecular brushes" can outperform nature under the highest pressures encountered within joints, with important implications for joint replacement surgery. Each 60-nanometre-long brush filament has a polymer backbone from which small molecular groups stick out; those synthetic groups are similar to the lipids found in cell membranes. "In a watery environment, each of these molecular groups attracts up to 25 water molecules through electrostatic forces, so the filament as a whole develops a slick watery sheath. These sheathes ensure that the brushes are lubricated as they rub past each other when pressed together to mimic the pressures at bone joints."Known as double-network hydrogels, the incredible strength of these new materials was a happy surprise when first discovered by researchers at Hokkaido in 2003. Most conventionally prepared hydrogels - materials that are 80 to 90 percent water held in a polymer network - break apart like a gelatin; the Japanese team serendipitously discovered that the addition of a second polymer to the gel made them so tough that they rivaled cartilage - tissue which can withstand the abuse of hundreds of pounds of pressure.
Bone morphogenetic proteins are growth factors released during embryonic development to induce condensation and determination of cells, during chondrogenesis. Noggin, a developmental protein, inhibits chondrogenesis by preventing condensation and differentiation of mesenchymal cells; the molecule sonic hedgehog modifies the activation of the L-Sox5, Sox6, Sox9 and Nkx3.2. Sox9 and Nkx3.2 induce each other in a positive feedback loop where Nkx3.2 inactivates a Sox9 inhibitor. This loop is supported by BMP expression; the expression of Sox9 induces the expression of BMP, which causes chondrocytes to proliferate and differentiate. L-Sox5 and Sox6 share this common role with Sox9. L-Sox5 and Sox6 are thought to induce the activation of the Col2a1 and the Col11a2 genes, to repress the expression of Cbfa1, a marker for late stage Chondrocytes. L-Sox5 is thought to be involved in embryonic chondrogenesis, while Sox6 is thought to be involved in post-natal chondrogenesis; the molecule Indian hedgehog is expressed by prehypertrophic chondrocytes.
Ihh stimulates chondrocyte proliferation and regulates chondrocyte maturation by maintaining the expression of PTHrP. PTHrP acts as a patterning molecule, determining the position in which the chondrocytes initiate differentiation; the SLC26A2 is a sulfate transporter. Defects result in several forms of osteochondrodysplasia
Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus. The first allele is dominant and the second allele is recessive. For genes on an autosome, the alleles and their associated traits are autosomal dominant or autosomal recessive. Dominance is a key concept in Mendelian inheritance and classical genetics; the dominant allele codes for a functional protein whereas the recessive allele does not. A classic example of dominance is the inheritance of seed shape in peas. Peas associated with allele r. In this case, three combinations of alleles are possible: RR, Rr, rr; the RR individuals have round peas and the rr individuals have wrinkled peas. In Rr individuals the R allele masks the presence of the r allele, so these individuals have round peas. Thus, allele R is dominant to allele r, allele r is recessive to allele R; this use of upper case letters for dominant alleles and lower case ones for recessive alleles is a followed convention.
More where a gene exists in two allelic versions, three combinations of alleles are possible: AA, Aa, aa. If AA and aa individuals show different forms of some trait, Aa individuals show the same phenotype as AA individuals allele A is said to dominate, be dominant to or show dominance to allele a, a is said to be recessive to A. Dominance is not inherent to either its phenotype, it is a relationship between two alleles of their associated phenotypes. An allele may be dominant for a particular aspect of phenotype but not for other aspects influenced by the same gene. Dominance differs from epistasis, a relationship in which an allele of one gene affects the expression of another allele at a different gene; the concept of dominance was introduced by Gregor Johann Mendel. Though Mendel, "The Father of Genetics", first used the term in the 1860s, it was not known until the early twentieth century. Mendel observed that, for a variety of traits of garden peas having to do with the appearance of seeds, seed pods, plants, there were two discrete phenotypes, such as round versus wrinkled seeds, yellow versus green seeds, red versus white flowers or tall versus short plants.
When bred separately, the plants always produced generation after generation. However, when lines with different phenotypes were crossed and only one of the parental phenotypes showed up in the offspring. However, when these hybrid plants were crossed, the offspring plants showed the two original phenotypes, in a characteristic 3:1 ratio, the more common phenotype being that of the parental hybrid plants. Mendel reasoned that each parent in the first cross was a homozygote for different alleles, that each contributed one allele to the offspring, with the result that all of these hybrids were heterozygotes, that one of the two alleles in the hybrid cross dominated expression of the other: A masked a; the final cross between two heterozygotes would produce AA, Aa, aa offspring in a 1:2:1 genotype ratio with the first two classes showing the phenotype, the last showing the phenotype, thereby producing the 3:1 phenotype ratio. Mendel did not use the terms gene, phenotype, genotype and heterozygote, all of which were introduced later.
He did introduce the notation of capital and lowercase letters for dominant and recessive alleles still in use today. Most animals and some plants have paired chromosomes, are described as diploid, they have two versions of each chromosome, one contributed by the mother's ovum, the other by the father's sperm, known as gametes, described as haploid, created through meiosis. These gametes fuse during fertilization during sexual reproduction, into a new single cell zygote, which divides multiple times, resulting in a new organism with the same number of pairs of chromosomes in each cell as its parents; each chromosome of a matching pair is structurally similar to the other, has a similar DNA sequence. The DNA in each chromosome functions as a series of discrete genes that influence various traits. Thus, each gene has a corresponding homologue, which may exist in different versions called alleles; the alleles at the same locus on the two homologous chromosomes may be different. The blood type of a human is determined by a gene that creates an A, B, AB or O blood type and is located in the long arm of chromosome nine.
There are three different alleles that could be present at this locus, but only two can be present in any individual, one inherited from their mother and one from their father. If two alleles of a given gene are identical, the organism is called a homozygote and is said to be homozygous with respect to that gene; the genetic makeup of an organism, either at a single locus or over all its genes collectively, is called its genotype. The genotype of an organism directly and indirectly affects its molecular and other traits, which individually or collectively are called its phenotype. At heterozygous gene loci, the two alleles interact to produce the phenotype. In complete dominance, the effect of one allele in a heterozygous genotype masks the effect of the other; the allele that mas
The metaphysis is the narrow portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, as it grows it ossifies near the diaphysis and the epiphyses; the metaphysis may be divided anatomically into three components based on tissue content: a cartilaginous component, a bony component and a fibrous component surrounding the periphery of the plate. The growth plate synchronizes chondrogenesis with osteogenesis or interstitial cartilage growth with appositional bone growth at the same that it is growing in width, bearing load and responding to local and systemic forces and factors. During childhood, the growth plate contains the connecting cartilage enabling the bone to grow. In an adult, the metaphysis functions to transfer loads from weight-bearing joint surfaces to the diaphysis; because of their rich blood supply and vascular stasis, metaphyses of long bones are prone to hematogenous spread of osteomyelitis in children.
Metaphyseal tumors or lesions include osteosarcoma, fibrosarcoma, enchondroma, fibrous dysplasia, simple bone cyst, aneurysmal bone cyst, non-ossifying fibroma, osteoid osteoma. One of the clinical signs of rickets that doctors look for is cupping and fraying at the metaphyses when seen on X-ray. Diaphysis Epiphysis Anatomy photo: Musculoskeletal/bone/structure0/structure2 - Comparative Organology at University of California, Davis - "Bone, structure"