Genetic burden test

The human genetic burden is a term set by the sum of man's harmful genes, genes that have lost their normal function by mutation. Recessive disease genes seem all people to be carriers of, perhaps in a number of one to five per person. There is a total of hundreds of such genes, but each one is fairly rare, the disease due to plant a double dose rarely. Overall, however, is Winkelstein-anomaly in app. 1% of all newborns. Great uncertainty prevails as to how often a gene mutates to a disease gene. Estimates suggest that you have overestimated the size of the mutation rate greatly, perhaps because the diseases that were selected were not representative and genetically homogeneous.

Mutation frequency of dominant single gene diseases is around a mutant gene per 100 000 gametes per generation for the most common diseases, but down to 1/10 - 1/50 of this for some others. The first corresponds to a new patient per 50 000 births in healthy families, and the last of a half-million birth per or less from others. This inequality has been difficult to understand, until option analysis of genes had now shown that this may be due to very large differences in the size of the plants. Hemophilia A is common, and 1/3 due to new mutations. The gene for hemophilia A is, however, spread over a distance of 200 000 base pairs on the X chromosome, although the coding part of the gene (the sum of exons) is only 7053 base pairs Due. Uncertainty in the measurement of mutation frequency, it is very difficult to prove even a 2-3-fold increase in frequency. It is perhaps also explained why so far has failed to prove that there has been any increase in germ mutations in those who survived the atomic bombs and the radiation in Hiroshima and Nagasaki in 1945. Mutation frequency can be increased by certain chemicals (mustard gas, 2-aminopurine, alkylating compounds, peroxides) or by radiation. The radiation dose required to double the frequency of mutations in humans, is probably 30-80 X-ray. The natural background radiation is 5.3 x-rays per 30 years.

The industrial culture has increasingly mutagenic effects on humans and other organisms. Use of X-rays in diagnosis and therapy, the use of chemicals in industry and agriculture will lead to an increase in the incidence of hereditary diseases, but we do not know to what extent. Since there are more people born on Earth in recent decades than the sum of all born before, even at a constant mutation rate have occurred several new mutations at this time than has occurred previously. The brand-new mutations with deleterious effects merely in the dual dose (recessive inheritance), we just know in the future if they come in a double dose or meet "old" widespread and therefore, more important mutations. It is accordingly, crucial for the future, how people will develop the disease will occur. If one together or being relegated to small groups (endogamy), we get an increasing burden of disease with the "new" diseases, poisons, we across regions, borders and continents, the diseases do not show up, and some "old" diseases diminish as we have seen in recent decades. "The colorful community" is therefore, the best out of our genetic diversity.
Read more

Specific Genetic Disorders

Properties not related to their specific DNA gene.

Many functional "anonymous" genes are found in the sequence database that ORFer (open reading frames, an open reading frame), which proves that there are functional genes. When you have found chromosomal localization of a Mendelian trait or disease, we can now take on ORFene and known genes in this area to find the mutation that proves the right gene. How it was found that the "new" gene BSCL2 for Seip disease.

The genetic maps of each chromosome have been determined by typing of genetic markers (polymorphisms) in families, while the physical genetic structure refers to the partitioning of chromosomes in cell cultures after irradiation (radiation mapping), to other forms of chromosomal abnormalities and to the cloning of large or smaller pieces of chromosomes in the DNA to "vectors," especially in yeast (YAC) and bacterial (BAC clones).

DNA variation as discussed above has led to detailed maps. It was in 1996 and systematically searching for and then family-tested and chromosome mapping 5264 dinucleotide (two-base pair) micro satellites (approached). The physical length of DNA which were over totaled 3.164 billion base pairs, while the genetic length (in percent crossing over) was 2730 centimorgan (cm) in men and 4397 cm in women. The difference is due to the smaller chromosomes are shuffled by the crosses in men than in women. Since 60% of chromosome sections had these STR markers that vary greatly in population by less than 2% cross-over distance, and only 1% of the genome had distances of 10 cms, allowing them approached us to find chromosomal localization to many more single affection's hijacker. The most detailed genetic map in humans is currently based on 143 Icelandic families tested for over 8000 micro satellite markers.

New discovery is that the crossover frequency in women varies much more than in men, and from pregnancy to pregnancy.
Read more

What is human genome

Human genome and Genki Arteta

Since the X chromosome in males alone, all the condition of sex-linked inheritance is due to genes on the same chromosome. In the 1930s it was found that color-blindness and hemophilia in the alike family came together largely in inheritance through females (who sticks his two Xer before egg formation), the plants were so close with each other that they were "genetically linked." The first coupling ratio of autosomes was discovered in 1951 by Jan Mohr (between Lutheran-blood type and secretary vileness). Only when these were shown connected to other inherited characteristics (an enzyme system and a serum protein), in 1983 show that these genes were on chromosome 19 in the same link group found him and later researcher's gene for a dominantly genetic muscular dystrophy myotonic. AB0-blood types were discovered in 1900, and in 1924 realized that there was a single pair of genes that determined the blood group variation. However, it lasted until 1975, before they knew gene locus for AB0 was on chromosome 9. It was an enzyme polymorphism (AK, adenyl kinase) was previously shown connected to the AB0 genes that allowed the mapping of the chromosome. In 1987, a dominant nerve disease (tuberous sclerosis) appended to this linkage group using DNA types.

Mapping of genes of the chromosomes was first recorded in the 1970s because of the hybrid cell technique, accelerated in the 1980s because of recombinant DNA techniques, and exploded in the 1990s because of the numerous micro-satellites (see above) and physical mapping methods. The hybrid technique use's laboratory produced mixed cells from two species, typically human and hamster or human and mouse. These cells have both species' chromosomes, but will gradually lose human chromosomes when they divide. One can then follow the loss of the human enzyme types in parallel with chromosome loss, and to determine how plants are enzymes. From the first mapping of a functional gene to a precise autosome in 1969, the number rose to approx. 250 in 1977 to approx. 600 in 1986. As of 1996, there were well characterized 3700 gene loci (locus is the same as the location for a gene on a chromosome) to their specific locations on chromosomes, of which 1049 had one or more mutations that gave single ticket disease, the other known due to the cloning of genes for proteins or the detection of genes by DNA sequencing (chromosome "walking"). During and after the sequencing of the total human genome (see Human Genome Project), you would think all of Mendelian inherited characteristics were gene identified, but this is far from the case. There is still a good number of cataloged Mendelian diseases or genome - that is evidence of environmental effects.

When a single ticket disease or gene as simple chromosome mapped by family method to a specific location on a chromosome, and also mapped to the same place the gene for a known protein or enzyme, the last a candidate for the disease. One can then look in the gene for a mutation to explain the disease. Through the human genome project, walk a different path, namely a direct DNA sequencing of a larger piece of chromosome, including the detection of coding DNA.
Read more

Chromosomal Abnormalities

Chromosomes can be studying in the cells during division, for example in bone marrow cells or cultured cells, most commonly in white blood cells that are stimulated to divide. At the appropriate color, methods appear chromosomes under the microscope as shown in the figure. The cells in the body of an individual contain, even so, set of chromosomes, and thus a full set of genes. However, some people have deviations from the normal set of chromosomes in their cells. Numerical deviations are most common, for example. Women with an auxiliary X chromosome as the sex chromosomes and chromosome number XXX in all the 47 this occurs in 1 of 800 girl births. It also women are born with only one X chromosome (45, XO, Turner syndrome, 1 in 3,000 girls), men with an extra X chromosome (47, XXY, Klinefelter syndrome, one of 400 boys), men with an extra Y chromosome (47, XYY, double-Y syndrome, 1 in 1000), and persons with Down syndrome who have autosomes No. 21 in the triple dose (47, trisomy 21, 1 in 1,000 births). Trisomy of other autosome's results in larger congenital malformations or is incompatible with life. This is reflected in a high frequency of chromosomal aberrations in cells from early spontaneous abortions.

The numerical deviation of the X chromosome had the little effect because each cell disabled their X chromosomes except one (lyonisering, first discovered by Mary Lyon in mice in 1961) therefore, the XXX-normal and fertile women.

Turner (XO) females lacking ovaries and secondary sexual development does not occur while the length of the growth is inhibited Klinefelter-(XXY) men missing who epithelial, and therefore, not developed. A slightly abnormal hormonal state often resulted evnukoid build with long limbs, wide hips and the development of breasts in light level. Furthermore, the psyche can be changed. Turner and Klinefelter syndrome shows that Y-chromosome in humans contains the male determining gene.

The XYY in males is generally increased length growth, and in some countries have found that XYY-persons cases occurring among criminals than in the general population. In trisomies are the normal gene in the triple dose instead of a double dose, and this leads to imbalance which we best knew from Down syndrome (trisomy 21). Only one autosomes, instead of two, does not provide a viable fetus. The reason for the numerical deviation of inheritance is that the two chromosomes in a pair of chromosomes do not split up as normal when the gametes are formed. This tendency increases with maternal age, in particular, under Norwegian law, women who become pregnant with 38 years of age (in our neighboring countries over 35 years of age) the provision of amniotic fluid in cell chromosome test early in pregnancy.

Structural chromosomal abnormalities are not frequent, but they are very important because the tendency to be an unbalanced chromosome ratio in the offspring can be hereditary. It is here on distinct chromosomes that have been cut, and where parts of different chromosomes have been spliced ​​together. Such chromosomes are often called the translocation chromosome (translocation, movement). As long as both trans-location chromosome's intent found in cells of an individual, are plants that normally inherit a double dose and the individual is healthy. In some of the offspring, however, chromosome distribution will be wrong, so there is partial trisomies or monosome, and this leads to birth defects or miscarriages. Approximately, 1-2% of people with Down's syndrome have this because chromosome 21 is involved in a translocation chromosome, which is balanced by a parent. There is no age effect. For parents who were young when they had their children with Down syndrome, it is therefore, particularly important that they be offered chromosome analysis, if they think of more children. This is recommended for all parents of such children.
Read more

Human population genetics


Population genetics study is based on that in different population's maps the frequency of various inherited properties, particularly particular affection's hijacker. It turns out that race differences largely depending on the alleles in single ticket systems have different frequencies in ethnically or geographically separate populations, and not due to the absolute absence or presence of "specific alleles" in one or the other population. Equality / inequality in gene frequencies has been used to determine the different population groups' relationship to each other, but it has also been shown that random fluctuations (genetic drift) and environmental factors (eg. Malaria: selection) can play a definite role in origins of inequality in gene frequencies. Cloning of genes and direct detection of rare mutations have led to that one can follow certain genes in populations and migration between countries more on this topic during genetic epidemiology.

The study of mitochondrial DNA has given strong support to the theory that Homo sapiens lived in Africa for at least 100 000 years and that maybe for some. 40 000 years ago a small group through the Middle East spread to Asia and Europe a long way more information about the history obtained by testing normal DNA markers around the unique mutations, the so-called haplotype analysis. That is how much you go down the DNA string that determines how far back in time you will get the story.

At the international "human diversity" project aims at collecting samples for DNA analysis of as many groups of people who have lived long, more or less isolated, in a place before isolates are completely dissolved. More marriages between counties rather than in the home county have led to a decline in rare recessive diseases. This reflects that we are probably descended from several different immigrant populations in the 10,000 years it has actually lived people in the country older people with mainly local ancestors in their DNA an information that will stretch far beyond the topical history books-in range. It is here in the order of the alleles in all DNA markers along the chromosome strings, which requires samples from two generations.
Read more

Multifactorial Genetic Disease

When you find irregular familial occurrence of a qualitative trait, the reason usually a combination of several single gene variations and environmental factors such as properties, for example. Congenital pylorus-stenosis (narrowing of the lower abdomen mouth), club foot and cleft lips with or without cleft palate, shows like a large variation in severity. They are also more frequent in the population than either single ticket diseases. In each family, there will not be so many with the disease as it is in families with single ticket disease.

Finally, one can prove the method of family how much of the variation of a quantitative trait, for example. Body height or intelligence, which is due to inheritance. Eugen Fischer showed in 1918 that the sum output of many individual genes, which we must assume is the specific allele in polymer systems, provides a quantitative normal distribution when each allele contributes moderately to the inheritance (polygenic or multifactorial inheritance).

Family studies can thus give us help when we want to estimate how much of the variation between individuals is due to polygenic inheritance, and how much is due to environmental factors. An example is that we are differently predisposed to ulcers. Some family data suggest that 2/3 of the variation due to environmental factors, and the third is due to polygenic genetic variation. For this polygenic disposition may be the height of 5% is attributed to the two known one-way systems: secretor vileness and AB0-blood group system.

People of blood type 0 (zero) has approx. 1.4 times as likely to develop ulcers in the duodenum that people with blood type A, B or AB. A person with blood type 0 that cannot secrete blood group substance in saliva, and gastric juice (nonsecretor) have a risk of duodenal ulcer, which is 2.5 times the risk of other types of people. Which gene's predisposing seems you can find on the determination of whether there is association (see below) between a single ticket system, and polygen affected property. When it comes to the disposal of the disease, such as increased disposition to develop cancer, it made great progress. When breast cancer is mutations in one of two genes that can cause an inherited disposition. Proven carriers will be followed up prevention. The same applies to family history of colon cancer.

The twin method was used already in the 1880s by Francis Galton. The method can be used for a relative assessment of inheritance versus environment causal factors. The twin method can, however, little or no extent, tell us something about the genetic mechanisms underlying the phenomena.
Read more

Mitochondrial diseases

Read more

Triplet diseases

The most single gene diseases cause that a gene has been changed in an easy way (replacement of one base to another, loss of or deposit of an extra base, etc.) then inherited in its altered from unchanged within the same family species as the disease itself uniform. Some diseases with simple dominant inheritance have shown considerable variation within the family. From the late l980's was the reason for this finding. Just outside the gene or paid within the gene is found a repeat of three bases.

The number of repeats in the normal population varies, but when the number rises significantly, it will disrupt the plant genetic function, increasing the number of repetitions wearing. It is therefore, a proliferation number of triplet repeats, which exceeds the threshold of disease. Under inheritance, it will rarely occur changes in the number of repetitions under normal conditions but when the repetition count is high and associated with disease symptoms, occurs more often changes in the number of repetitions between the generations. Such triplet-change has been called dynamic mutations, mutations that constantly change.

In Huntington's disease is the base sequence (triplet ten) found repeated from 36 to over 121 times, while normally only find that repetitions are less than 34 at a normal repeat length jumps up to over 36 is not actually registered (that is extremely rare). While those with low symptoms and late onset of Huntington has a "premutation" between 36 and 50 repetitions easier / more likely to jump up in higher numbers to the next generation (less often, they are shorter) and therefore, give serious Huntington with an earlier onset. The table shows a similar relationship with the dominant myotone muscular dystrophy, and by the sex-linked fragile X syndrome (mental retardation in males).

The number contains discovered dominantly expressed triplet diseases is increasing, and has so far found mostly in the nervous system genetic disease, but also a recessive neurological disease (Friedreich's ataxia) is due more frequently a triplet-repeat than normal point mutations.
Read more

Genetic diseases in humans


Extremely short finger was the first property that was proven to have Mendelian inheritance in man (1903). Some other examples of autosomal dominant characteristics are given in the table, including the Huntington's chorea (hereditary Vitus's dance, Setesdal Rykkja, first described by the district Lund). The first diseases recognized to have recessive inheritance in man, was the type of congenital metabolic disorders, first described in 1902 and 1908. Otto Lous Mohr published in the period 1920-1944 Mendelian inheritance of a variety of conditions, including evidence for recessive inheritance at Foaling disease.

Asbjorn Foaling described in 1934 the disease phenylketonuria (PKU or Foaling disease). The disease is caused abolished function of a liver enzyme that normally transferred the amino acid phenylalanine to tyrosine. In PKU, patients do not happen, and it is formed rather than metabolic products that lead to mental disability and characteristic movement disorders. Today revealed PKU blood samples of newborns, and by a special diet could be retarded avoided. Arve plant was in the 1980s were cloned by the classical method? First determined amino acid sequence in enzyme protein, as stock is a small piece of DNA from the genetic code, then we use this DNA piece (the probe) to fish out the correct DNA snippet from nuclear DNA and map the rest of the gene. A portion of the gene was "in situ hybridized" on chromosome preparations and its localization on chromosome 12 identified. In 1999 found 33 unusual mutations in the Foaling (PAH) gene, and the geographical distribution is different for most people.

Normal albinism is not only one but two independent recessive diseases. The one is the lack of normal tyrosinase activity that makes the pigment melanin is not formed at the other the lack of a P-protein. The two types can be distinguished by tyrosinase test the hair from albino individuals, or by detection of the mutation in their gene. This is important for genetic counseling.

Among examples of hereditary diseases first described, are also the dominant Müller-Harbitz disease (1930) (hyper cholesterol) and recessive conditions Norum and Gjone Disease (1967), Refsum's disease (1946), Seip Disease (1959) , Aagenæs' disease (1968), and a variety of metabolic diseases discovered since the 1970s by L. Eldjarn, E. Jellum, EA Kvittingen and O. Stokke. For several of this is the gene cloned and the mutations found in the same order: LCLR (chromosome 19), LCAT (chromosome 16), PAHX (chromosome 10 and others), BSCL2 (chromosome 11, codes for the protein seipin for MARTIN SEIP ). By Aagenæs' disease (chromosome 15) and by ichthyosis-prematurity syndrome (chromosome 9, see the map) is chromosomal localization, but not the genes found (per 2004).

The most frequent of the serious recessive diseases among northern Europeans are cystic fibrosis. The gene for this was found at position mapping: In 1985, they found genetic markers that followed the disease inheritance (genetic link), afterwards mapped the Mon a linked DNA marker to chromosome 7, then followed an intense search along the chromosome up to date new gene was proven to be the right (1989). When the gene was cloned so, one could sequence the DNA and find the mutations. It is now found over 300 different mutations in the gene; one of thirty plants carries and 66% of those carrying a particular mutation. While every 2000. Birth or more with us gives a homozygous (ill) children, the disease is almost unknown in the Finnish population.

Already in 1917 wrote a doctor (Magnus) that a healthy Mothers-related fish Ehud (ichthyosis) with several men had caused X-linked inheritance. This and other observation were overlooked until sex-linked ichthyosis was "proven" and widely recognized in the l960's. An example of the dominant X-linked gene is what gives the vitamin-resistant rickets. Most of the disease and the X chromosome has recessive effects; that is, almost exclusively boys get the disease (sex-linked inheritance). Two severe hemophilia, hemophilia A and hemophilia B is caused by recessive plants in each of their location on the X chromosome. Both facilities are now cloned and known in detail, as DNA studies can be used for precise genetic counseling. Red and green color blindness are sex-linked, but the two tightly coupled genes that are so frequent (8% of men) that women sometimes have facilities on both their X chromosomes and therefore, color-blind (0.2% of women). Pediatrician Arne Nja described 1946 as the first, that some form of gargoylism was sex-linked hereditary, but it was Hunter, who later had his name attached to the disease. Furthermore, first described is Aarskog Syndrome (1970), where the gene on the X chromosome was found at position mapping in 1994.
Read more

Conserved sequences

Non-coding DNA, highly conserved unique sequences (HCS)

Of recent date is the discovery that in the non-coding DNA is stretches of unique DNA sequences that are considerably conserved in evolution:

they show as little variation as the unique DNA sequences to the coding DNA for functional genes.

These Highly conserved Sequences, which lacks the known elements required by the coding DNA, is not known the importance of (2005), but they may contain information of fundamental biological importance.
Read more