The concept of heredity can be traced back to ancient Greece era of Hippocrates (an ancient Greek doctor, the founder of western medicine, about 460 ~ 377 BC). At that time, people had realized that certain diseases could be transmitted in the family. About 1500 years ago, Talmudic stipulated that “bleeders” could be exempted from circumcision, which proved that people had already known the genetic rule of hemophilia.
Hemopilia A is a kind of genopathy. Patients with hemophilia A will suffer from coagulation defect and often keep bleeding in the wound. Clotting mechanism includes a series of cascade reactions in the process of proteolytic enzyme activation, involving ten blood coagulation factors. The clotting factors Ⅷ and Ⅸ located in X chromosomes. The disease of Hemophilia A is due to one gene mutation of any of these two chromosomes.
Heredity refers to the phenomenon that there are similarities between filial generation and parental generation in the process of reproduction, and the significance of it is to ensure a stable and continued generation. For example, two kinds of tongues: rolling tongue (AD) and smooth tongue(AR); two kinds of forehead hairlines: “V” hairline (widow's peak) and “line-shaped” hairline. hereditary character is determined by genes. Macroscopic features can be distinguished with naked eyes, while physiological and biochemical characteristics cannot. For instance, there are four blood types: A, B, O and AB; The ability to taste Phenylthiocarbamide (PTC) - (dominant) taster can taste the bitterness of it while the (recessive) taste blindness people cannot. Variation refers to either the difference between filial generation and parental generation, or among offspring. The significance of variation is evolution.
Genetics is a study about essence and rules of heredity and variation. Medical Genetics is a study about the relationship between human diseases and genetics, which is the application of genetic knowledge in the field of medicine.
Medical Genetics puts emphasis on the study of etiology and pathology of genopathy (genetic diseases). It aims to study the occurrence mechanism of genopathy, transfer law of genetic diseases as well as its relationship with clinics. Its purpose is to reduce the occurrence rate of genopathy and to improve the quality of human health. Genetic Medicine puts emphasis on clinical service for the patients with genetic diseases, including prevention, diagnosis, treatment, screening, counseling and follow-up of genetic diseases, for the purpose of reducing the pain of patients and helping them enjoy a happy life.
The significant events in the history of Medical Genetics:
| Year | Significant events | Main contributors |
|---|---|---|
| 1866 | The Law of Segregation and the Law of Independent Assortment were revealed | Gregor Johann Mendel |
| 1910 | The Law of Linkage and crossing-over in Gene was put forward | Thomas Hunt Morgan |
| 1859 | Alkaptonuria disease was the first diagnosed Congenital Metabolic disease | Boedeker |
| 1901 | Alkaptonuria was a recessive disease (AR) | Garrod |
| 1903 | Brachydactyly was the first case of human dominant inheritance (AD) | Farabee |
| 1949 | the concept of molecular disease was pointed out | Pauling |
| 1956 | The number of chromosome (46) was identified, marking the beginning of the history of cytogenetics | J．H．Tjio |
| 1953 | DNA double helix model was revealed, opening up the beginning of molecular genetics | Watson and Crick |
| 1991 | Human genome project (HGP) started | the US, the UK, Japanese,France, Germany, and China |
| 2004 | Nature revealed 3 billion base pairs of the whole human genome sequence | the US, the UK, Japanese, France, Germany, and China |
The disease caused by genetic factors is called inherited diseases or genetic disorder. Genetic factors can be the changes in structures and functions of genetic material from zygotes or germ cells, and can also from somatic cells.
Genetic Disorder can be transmitted vertically from one generation to the next. This transmission does not transmit the disease itself but the mutated genetic materials which can cause diseases. It is the basis of genetic material that causes the same genetic disorder in both offspring and parental generation.
There is a certain quantitative relationship between patients and normal people. We can expect the risk of recurrence through understanding the genetic characteristics and occurrence regularity of the diseases.
Congenital disease refers to the disease which an individual is born with. Many genetic disorders have the characteristic of congenital, such as Alkaptonuria and Albinism. But not all the congenital diseases are inherited diseases. For example, a pregnant woman suffers from rubella virus, resulting in her child born with congenital heart disease, which is acquired.
Familial disease refers to the diseases that has familial aggregation phenomenon, which means two or more members in a family suffer from the same sort of disease. Most of the genetic disorders have familial features, such as Huntington disease. But not all the familial diseases are inherited diseases. For example, if a family lacks of vitamin A for a long time, several people in the family is likely to suffer from nyctalopia, which is caused by environmental conditions instead of genetic disorders.
Human prion disease is a kind of disease that is hereditary and infective. At present, it is considered that the cause of brain tissue becoming spongy is PrP gene mutation, which can lead to PrP misfolding or making other protein misfolding, finally resulting in brain dysfunction. However, misfolding prion protein (PrP) can spread in some ways to normal cells, making normal proteins misfold and cause disease, which is known as protein folding disease.
(1) Single-gene disorder: caused by mutation of one gene
(2) Polygenic disorder: caused by combined action of several genes and environment
(3) Chromosome disorder: caused by structure or number change of autosome or allosome
(4) Somatic cell genetic disorder: caused by mutation of somatic cell genetic material, including malignant tumor, immune deficiency disease, and senescence.
(5) Mitochondrial genetic disorder: caused by mitochondrial DNA defection, transferred with mitochondria, presents as cytoplasmic inheritance.
Online Mendelian Inheritance in Man (OMIM) is the most authoritative database in Medical Genetics, it is honored as the “Bible” of Medical Genetics. The website is http://www.ncbi.nlm.nih.gov/omim.
When a man is healthy, there is a balance between metabolisms which is controlled by human genetic structure and the surrounding environment. The defect of the inherited structure or the significant change in the environment can break the balance and cause disease. The occurrence, development and prognosis of the disease are affected by the hereditary factors and environmental factors. However, these two factors have different proportions in etiology in different diseases.
** (1) Disease occurrence is totally determined by hereditary factors without the impact of environmental factors. **
For example, single-gene disorder Hutchinson-Gilford Progeria Syndrome (HGPS, AR), hemophilia A (XR), and some chromosomal diseases.
** (2) Hereditary factors play a decisive role in causing diseases, and environmental factors play an incentive role.**
For example, eating food which is rich in phenylalanine can cause Phenylketonuria (PKU), a kind of single-gene disorder. Phenylalanine hydroxylase (PAH) mutation can result in lack of phenylalanine hydroxylase and metabolic disorder of the phenylalanine, leading to the opening-up of the metabolic shunt, which transform phenylalanine to phenylpyruvic acid. Accumulation of phenylpyruvic acid can cause nervous system damage, mental retardation and the infant’s urine has a special smell of rat urine.
And for another example: Glucose-6-phosphate dehydrogenase deficiency, which is also called favism. After eating broad bean, or touching broad bean pollen, or taking oxidation drugs, patients with this kind of disease may suffer hemolytic anemia. G-6-PD has the function of preventing normal erythrocyte from being oxidized. Mutation of G-6-PD gene result in lack of G-6-PD, leading to haemoglobin denatures and hemolysis.
(3) Both inherited and environmental factors play roles in causing diseases, but the degree of heritability varies in different diseases.
If the heritability degree is high (above 70%), it means hereditary factors play an important role in causing the diseases, such as: hare lip, rictus lupinus, congenital constriction of pylorus, schizoaffective disorder and schizophrenia.
If the heritability degree is low (below 40%), it means environmental factors play an important role in causing the diseases, such as: congenital heart disease, duodenal ulcer and peptic ulcer.
If the heritability degree is between 50% and 60%, it means both inherited factors and environmental factors play the same important roles in causing the diseases, such as: spinal bifida, anencephalus, hypertension and coronary heart disease.
The occurrence of the disease depends on environmental factors and it seems has nothing to do with the impact of inherited factors.
(4) Environmental but hereditary factors play a decisive role in causing diseases
For example, trauma (burn, wound, etc.), intoxication, infectious disease (avian flu, SARS), nutritional disease, etc. These diseases do not inherit but there is a certain inherited basis, and the repair and prognosis of injury varies from one to another.