Introduction to genetic disorders

Hello everyone! Nice to you see you! Today is the first lecture of

the section 2: How to identify a disease? I am an instructor, Chia-Ling Hsieh, from the PHD program of translational medicine, Taipei Medical University, Taipei, Taiwan. Today’s topic I will separate into two talks,one is general introduction of the genetics disorder, and the second one, we will review and introduce some methodologies which can be used to diagnosis the genetics disorder.

From the beginning, we will review the some concepts of the genetics. As we know, the human being, like you and me, we have a total, 23 pairs of chromosomes. The total number is, of course, 46. Our parents contribute the chromosomes, half and half. This genetic information is located on the gene and this gene you can find on the chromosome. Each chromosome contain 2 copies of the gene we also call the “alleles”. This allele will determine the phenotype of our behavior, and this behavior and the phenotype can transmit from the parents to their children. All the alleles, since they contain the two copies of the gene, of course, maybe the one gene will become the dominant.

So if this kind of DNA sequences is expressed, they will take over the others and expressed the phenotype. Sometimes, the gene is called “recessive” it means two copies of the gene should be expressed together to determine the phenotype. But sometimes, the two gene, even the, sequences is different they can express simultaneously. The example, like that, we eat the corn that have different colors, they have the white, they have the red, they have the green, colors. Each color, is determined by one allele of the gene. So if you see the one corn have two colors, it means this, the gene of two alleles is codominant. Now we are talking about what is genetic disorder.

A genetic disorder is the disease caused by an abnormality in an individual’s DNA. This kind of abnormality can be very small, as a single base mutation in just one gene. The mutation comes from all the parent’s DNA so if we have this kind of disorder are also called the mendelian disorder. It means this defect DNA is inherited from our parents, so it occurs when he was born. The other type of disorder is called complex disorder. This disorder actually is not a defect on DNA when we was born. It actually is caused by the acquired mutation.

This mutation is caused by a lot of environmental factors such as we drink a lot of alcohol or smoking, or even environmental pollutions like the hormone. This kind of the inducer will trigger the mutation during our lifespan. This is more complicated, involves a lot of factors so it is called complex disorder. What kind of the factor will cause genetics mutation? The mutation type we can categorize into three types of disorder. One is mutations, very small in one gene. Even is in the dominant allele or in both the recessive allele. Sometimes it happens on the sex chromosome, like the X chromosome or Y chromosome.

And because these the mutation is only located on one gene, so is also called the single gene disorder. This kind of disorder actually is very rare in the population. It only takes place about 1% of the disease. Second one is the mutation happened in not only one gene but also a large portion of the genes. This mutation, actually in the beginning, didn’t cause the disease. It’s just the sequences differences between the individuals. But because the sequences differences so they have a different susceptibility to environmental factor As I mentioned, drinking alcohol or smoking will trigger these variations to become the most sensitive to mutation that will cause the disease.

And because this is combined the genetics information of sequences and the environmental factors so this called the multifactorial disorder. This kind of disease is very popular in the genetic disease. Like a lot of the patients suffer from the cancer and the diabetes. These two kinds of disease are caused from the multifactorial disorder. The last one, is even bigger mutation in the gene. It happens on the whole chromosome or large portion of chromosome is being changed. And this kind of change will alter our gene dosage in the expression level. It’s called the chromosomal abnormalities. Of course this kind of chromosomal abnormalities is also passed during the inherence so there is only vary rare population have this kind of disease.

It only occurs about 0.6 percent of the disease will be caused by these chromosomes abnormalities.

I’d more detailed to introduce the single gene disorder. As I say, the allele’s characteriesticscan become the dominant or recessive, and the sex linkage the chromosome. If the mutation is occurred on the dominant allele, only one copy the mutation can alter the all phenotype and got the disease. For instance, the huntington’s disease. If these mutation occurs on the recessive chromosome, they will be required for two copies the gene simultaneously mutations. This kind of example of disease such as cystic fibrosis. If the mutation happens on the sex chromosomes, for instance, in the male or the boy, we know their sex chromosome contains one copy of the X and one copy of the Y.

So if the mutation is happened on the X chromosome, they cannot like the girl to have another normal X allele can compromise these defects, so they will cause the disease. For instance, the Duchenne Muscular Dystrophy is an example of this disease. About a large portion of whole chromosome abnormality, It can be by the change in the number or even structural. Why the number will change during the birth ? It is because when the cell undergo meiosis, the chromosome cannot be equally separated into the two offspring cells. In this way, one cell will get maybe extra one more or even two copy more of the chromosome. And the other one will lost or miss copy of chromosome.

If we have the three chromosome together, as I say, in the normal population, the chromosome is paired, but you have got the one extra copy is called the “trisomy”. If you get the two extra copy become the four homologous chromosome, this called “tetrasomy” chromosomes. On the other hand, if you delete or lose one copy of chromosome, you only get one copy, this called “monosomy”. Other than the number can be changed causing the disease, of course, in the small portion of chromosome can also be changed. For instance, the gene on the portion of chromosome can be missing or lost. On the other hand, maybe they have gotten the duplicate.

Sometimes these gene when they do the replication, they will flipping over so the orientation will be opposite and this called the “inversion”. The fourth type of structure of the abnormality is because due to the two different chromosome, putting them close together they will change the portion of the chromosome to the other chromosome, so they will cause the gene “translocation”.