Somatic aneuploidy to Human Physiology
Somatic Aneuploidy to Human Physiology
Introduction
Before we discuss somatic aneuploidy, there is important thing to know: Because almost mechanisms of relation between mitotic aneuploidy and its phenotype are unclear, there is no direct linkage from mitotic aneuploidy to phenotypes from now on, it means that only the certain abnormal number of chromosome doesn`t indicate the phenotypes - in other word, there are many factors about the phenotypes included aneuploidy.
The phenotypes of somatic aneuploidy are largely organized as 3 types in my search.
Result
1. Cancer
In healthy human, somatic aneuploid cells exist at low frequency in almost body cells, but can have high frequency in certain part. Such high frequency of the aneuploidy shows tolerance that ignore some degree of genetic error. Human Cancer Cells can have Increased Tolerance to Aneuploidy, it means that the proportion of aneuploid cell of cancer cell is much higher than normal cell.
Leukemia, cancer of white blood cell, has two types related to mitotic aneuploidy in human : B-cell chronic lymphocytic leukemia, Acute myeloid leukemia
B-cell chronic lymphocytic leukemia(B-CLL), known as chronic lymphoid leukemia(CLL) is most general type of leukemia in adult. This is related to trisomy of chromosome 12
Acute myeloid leukemia (AML), known as acute myelogenous leukemia or acute nonlymphocytic leukemia (ANLL), is a cancer of the myeloid line of blood cells. AML occurred by rapid growth of abnormal white blood cells, which accumulate in bone marrow and interrupt production of normal blood cells. This is related to trisomy of chromosome 8
2. Brain disorder
In development stage of normal brain, aneuploidy is high rate as 33% of all brain cells, but aneuploidy of adult brain is low as 10%. Abnormal brain have also high rate of aneuploidy in adult cell compared to normal brain. It may be because the brain needs to use the somatic aneuploidy to make and maintain the neuronal network in development stage, but it doesn`t have to generate somatic aneuploidy according to aging.
In the result of the somatic aneuploidy, mosaic trisomy 21 exhibiting milder symptom exist as subtype of down syndrome(trisomy of chromosome 21). The additional chromosome 21 give serious effect to brain function and morphology about the down syndrome.
Alzheimer disease also occurred from mosaic chromosome 21 aneuploidy.
Ataxia telangietasia, neurodegenerative disease in early childhood, is related to mosaic aneuploidy of chromosome 14
3. Muscular disorder
One of the muscular disorder, muscular dystrophies(MD) is inherited disorder characterized by muscle wasting, weakness and replacement by adipose and fibrous tissue in human. The MD has several kinds such as duchenne muscular dystrophy(DMD) and limb-girdle muscular dystrophy type 2A(LGMD2A), limb-girdle muscular dystrophy type 2B(LGMD2B), limb-girdle muscular dystrophy type 2I(LGMD2I).
In the DMD muscle, chromosome 2 and 19 are both tetrasomies.
In LGMD2A muscle, chromosome 2 and 19 are both trisomies and chromosome 13 has aberrant counts.
In LGMD2B muscle, chromosome 2 and 19 are both monosomies -
In LGMD2I muscle, chromosome 2 and 19 are both trisomies.
As you can see below figure, the frequency of the aneuploidy of MD is higher according to aging.
Conclusion
In the 3 types of the phenotypes, I discovered two things in common. First, the proportion of aneuploidy is higher according to aging. Second, there is a tolerance that aneuploidy cell is possible to exist in some degree on the cells. Based on two common things, I can make a hypothesis: some degree of aneuploidy cell need for cellular mechanism like homeostasis, it means that it is important to maintain the balance between normal cells and aneuploid cells, and the possibility of disease exist not only when the aneuploidy cells are much higher compared healthy human but also when the normal cells are much higher.
Reference
6. Daniela Cimini, Virginia Tech, United States of America. Elevated Tolerance to Aneuploidy in Cancer Cells: Estimating the Fitness Effects of Chromosome Number Alterations by In Silico Modelling of Somatic Genome Evolution. PLoS genetics 2013;7:24.