What is human genome?

Human genome is the complete set of DNA (deoxyribonucleic acid) in human body. The DNA contained within each of body cells. The DNA carries the signals to build and maintain the body cells to function so that the heart will keep pumping, brain will keep thinking and bones will keep growing.
 

Overview and History of Human Genome Project

The Human Genome Project was the natural culmination of the history of genetic research. Alfred Sturtevant, an undergraduate student in Thomas Hunt Morgan’s laboratory, found that he could map the locations of fruit fly (Drosophila melanogaster) genes whose mutations the Morgan laboratory was tracking over generations. This is the tremendous start of gene mapping and finally leads to the human genome sequencing project.
 
When the Human Genome Project started in 1990, the researchers had set a goal to complete the project within 15 years but completed it in 2003, with two years to spare. During that time, many volunteers gave blood to provide their DNA as a contribution for the HGP. However, the labels on the blood tubes were intentionally removed to protect the privacy of the donors. Therefore, the final human genome sequence which has been published in 2003 is a combination of many of the donors’ DNA. The researchers had found that 99.9% of everyone’s DNA sequence is exactly the same. However, there are still some tiny fractions of genome that varies among humans. These variations are very important and make all humans unique in physical appearance like colour of eyes and even influence the risk of disease and the response to drugs. Even so, the genome is just one part of the amazing puzzle of human. Lifestyle and environmental factors do influence humans’ health condition too.
 

Contributions of Human Genome Project

By knowing this, the successful of HGP to sequence human genome has made the job of finding genes that cause some genetic diseases easier. The researchers hope that they can find out the genetic basis of other diseases such as heart disease, diabetes and even mental illness so that the drugs and treatments that specifically target these diseases can be designed properly. For example, there are some genes that involved in cancer had already been identified and make the treatment designed much easier.

What have been done in Human Genome Project?

In Human Genome Project, the researchers have deciphered the human genome in three major ways:
 
i. The sequence of all DNA bases in human genome.
 
ii. Maps that show the locations of genes for major sections of human chromosomes.
 
iii. Linkage maps which inherited traits especially those for genetic disease can be tracked over generations.
 
There are about 20,500 human genes revealed in Human Genome Project. This finding appeared to be significantly fewer than previous estimates, which ranged from 50,000 genes to 140,000. This final human genome sequence has given the world a resource of detailed information about the structure, organization and function of the complete set of human genes. This can be considered as the basic set of inheritable information for the development and function of a human being.
 
According to Francis Collins, the director of National Human Genome Research Institute (NHGRI), the genome could be imagine as a book with multiple uses. He said: “It’s a history book – a narrative of the journey of our species through time. It’s a shop manual, with an incredibly detailed blueprint for building every human cell. And it’s a transformative textbook of medicine, with insights that will give health care providers immense new powers to treat, prevent and cure disease.”
 
The Human Genome Project had created many tools that can be used in characterize the genomes of other organisms used extensively in biological research. For examples, mice, fruit flies and flatworms are the model organism that can be used to identify the sequence or function of a homologous (similar) gene in human beings.
 
In conclusion, the Human Genome Project might appear as a perfect project at the first glance. Most probably is the genome was successfully sequenced and the involvement of the government in the project. Yet, the ultimate success of HGP still remains unclear.
 
Reference: National Human Genome Research Institute
 

Is Human Genome Project really beneficial to humans? Leave your precious opinion to start the discussion.

Human Genome Project – Find out Human Database is a post from: Cytogenetics and Cancer Research

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The Angelman syndrome clinical diagnosis is heavily dependent on the combination of some common behaviour like excessive laughter, apparent happiness with tremulous movements and gait ataxia (lack of coordination of muscle movement). Usually, the normal prenatal and birth history do not provides any clues in diagnosis of AS in Cytogenetics. CT scans, laboratory tests of blood and urine are usually normal including metabolic screening. Consequently, it is difficult for the clinical experts to encounter the AS especially when the child is less than 12 months of age. It is because the tremulous movements, ataxia and severe lack of speech may not be apparent during that time.
 
There are many common features of Angelman syndrome.

i. Severe speech deficit (usually absent speech)
 
ii. Mental retardation
 
iii. Microcephaly (small head)
 
iv. Seizures (convulsions in which AS patient’s body shakes rapidly and uncontrollably)
 
v. Developmental delay
 
vi. Feeding problems
 
vii. Hypopigmentation (the loss of skin color)
 
viii. Frequently drooling
 
ix. Tend to put objects in mouth
 
The facial features general physical appearances are generally normal for the individual of Angelman syndrome. As the child with AS growing up, the correct diagnosis may become evident when speech is essentially absent and the attempts at walking are compromised because of sever ataxia. In addition, the seizures will occur more frequently after 1 year of age.
 
In conclusion, the individual of Angelman syndrome may be hyperexcitable with excessive laughing, grabbing and pulling to engage others. They are just like the ‘Angels’ who always bring happiness to people. Usually, the parents may be the first to suggest the possibility of Angelman syndrome. Thus, earlier detection of this genetic disorder may help the children to overcome the learning problem through the assessment from the clinical experts.
 

My ultimate hope is this Cytogenetics and Cancer Research blog can really help in increasing the awareness of people about the genetic disorders and cancer.

Angelman Syndrome – Angel-like Genetic Disorder is a post from: Cytogenetics and Cancer Research

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Prader-Willi syndrome is the most common genetic cause of marked obesity in humans according to Cytogenetics. It is a complex disorder with cardinal features of
 
i)    Infantile hypotonia (low muscle tone)
 
ii)   Mild growth retardation
 
iii)  Frequent occurrence of breech presentation (baby enters the birth canal with the buttocks or feet first)
 
iv)  Small hands and feet with gracile and tapering fingers
 
v)   Microcephaly (smaller head)
 
vi)  Almond-shaped eyes
 
vii) Mental deficiency (average IQ of 65)
 
viii) Short stature and so on.
 
From the age of about one and half years onward, hyperphagia becomes a serious problem, leading to gross obesity. Due to hyperphagia and gross obesity, diabetes often sets in during adolescence or later. Epilepsy is found in a minority of cases. Mental development is characterised by moderate to severe retardation with tendency to behaviour disorders, especially reactive to food deprivation. Patients with this syndrome may need specialists for assessment and treatment of their behavioural and learning problems, at the beginning of childhood. Prader-Willi syndrome is present in all races and ethnic groups and most cases are sporadic.
 
In conclusion, Prader-willi syndrome is a genetic disorder that needs treatment and assessment to overcome the learning problem and obesity problem of the patients. I will write a series of Prader-Willi syndrome in this Cytogenetics and Cancer Research blog in order to give people a clear mind about this syndrome. Stay tuned!

Prader-Willi Syndrome – Genetic Disorder That Cause Obesity is a post from: Cytogenetics and Cancer Research

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Meiotic Nondisjunction Causes Autosomal Aneuploidy

The origin of autosomal aneuploidy is because of meiotic nondisjunction. The meiotic nondisjunction is random for all autosomes except for chromosome 21. Chromosome 21 has shown the highest frequency of autosomal aneuploidy.
 
According to cytogenetic studies, the incidence of autosomal aneuploidy in spontaneous abortuses (die before birth) is much higher than incidences in newborns. So, what is the case for aneuploidy actually observed in spontaneous abortuses or liveborns? All trisomies for all autosomes have been reported in spontaneous abortuses. The fetal only can survive if and only if the trisomies are in mosaic form. However, there are still many exceptions for the trisomies 13, 18 and 21. Some of the foetus still can survive even though the trisomies 13, 18 or 21 are in nonmosaic form.
 
Why the frequencies of trisomy for each chromosome might be similar at the time of conception but differ greatly among abortuses and liveborns especially for trisomy 21? It can be explained by the devastating effect of chromosomal imbalance. Most of the autosomal aneuploidies are very deleterious and lethal in the pre-embryonic stage. As a result, those abnormalities are unrecognized and, therefore, unstudied spontaneous abortions.
 
Furthermore, the lethality of a particular autosomal aneuploidy is related to the gene content of the particular chromosome. Aneuploidies for the gene rich chromosomes are less likely to survive. However, the less gene rich chromosomes like chromosome 13, 18 and 21 are more likely to survive to term.
 
Anyway, we will just focus on those observed in liveborns for the autosomal aneuploidy in Cytogenetics. I will talk more details about the monosomies and trisomies in my future post. Stay tuned!

Autosomal Aneuploidy – Cytogenetic Abnormalities is a post from: Cytogenetics and Cancer Research

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Clinical Value of Cytogenetic Studies in Malignancy Cancer

Recently, there has been a significant progress in knowledge of the recurrent abnormalities in many of solid tumors as well as hematologic malignancies. Consequently, the clinical value of cytogenetic studies in cancer malignancy has been appreciated after the cytogenetic studies of some solid tumors moving out of cancer research environment.
 
Apart from this, there would be little clinical value in doing cytogenetic studies in cancer malignancy if all the patients with a particular cancer died. The researchers only manage to probe the origins of cancer for those patients. However, after researching in all tumors type by using cytogenetic technique, the presence or absence of many of the genetic abnormalities found has been related to different responses to treatment. Since that, the genetic and cytogenetic studies start to be recognized as important and one of the best choices of treatment for a cancer patient.
 

Cytogenetic Studies Helps Diagnostic Investigation in Malignancy Cancer

Consequently, cytogenetic analysis of cancer malignancy is considered to provide rapid, accurate and specific results to aid the clinical professionals. This can help to choose the most appropriate type of treatment to the cancer patient in shorter time. However, John Swansbury stated that the diagnosis of a malignancy can be traumatic, and an accurate and early indication of every patient’s prognosis is valuable.
 
In conclusion, a cytogenetic study remains an essential part of diagnostic investigations of every patient with hematologic malignancy and certain solid tumors without denying the valuable contributions made by other genetic assays.

Reference: Methods in Molecular Biology, vol. 220: Cancer Cytogenetics: Methods and Protocols. Edited by: John Swansbury © Humana Press Inc., Totowa, NJ
 

Do you know more about cytogenetic studied on malignancy? Come and share with us.

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Cytogenetic Studies in Malignancy Cancer is a post from: Cytogenetics and Cancer Research

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1. Enhanced Selective Miscarriage of Trisomy 21 Conceptions by Older Mothers

Analysis of the data shows that Trisomy 21 occurs in about 1 per 200 2000 of the births to mothers aged 18-24. The rate gradually increases in frequency to 1 per 300 births to mothers between 25 and 35. The rate continues to increase to 1 per 100 births to mothers at age 45 or older. Therefore, people start to come out with the hypothesis that is enhanced selective miscarriage of 21 trisomic conceptions by older mothers. This hypothesis claims that the increase of mother’s age is directly proportional to the enhanced selective miscarriage of trisomy 21. The non-disjunction seems to occur more frequently for older mother. During the meiosis, the older female’s gamete cell will miscarry two chromosome 21. Fertilization between this abnormal ovum with the sperm will cause the Down Syndrome.
 

 

2. Less Effectiveness for Oocyte Selection in Older Mothers

Another hypothesis is the decrease of effectiveness for oocyte selection in older mother. Oocyte selection is the process that determines which oocyte can enter the next stage of development. Only the normal oocyte will be selected and the abnormal oocyte will be eliminated. If the effectiveness of oocyte selection decrease because of the older age, the abnormal oocyte might be selected. This will cause the non-disjunction occur during the meiosis.
 

3. Sperm Aging Hypothesis

Some scientists raised up the sperm aging hypothesis claiming that the non-disjunction occurs because of the influence of sperm aging in male genital tract.
 

4. Chiasma Hormonal Hypothesis

Some scientists prove that there is an interaction between the hormonally governed rate of meiosis and the timing of chiasma terminalisation. The changing hormone levels during the menstrual cycle not only stimulate recommencement of meiosis in ovum, but also control the rate of meiosis through a limiting substance. The hormone levels and the length of the cycle will change with advancing age of the mother. Therefore the meiosis will slow down and chiasma frequencies decline. As we know, chiasmata is important for the meiotic chromosome bivalents to held together during meiosis. It will cause the premature separation during terminalisation. This can lead to Down Syndrome.
 

5. Consanguineous Parents Hypothesis

Some people said that the Down Syndrome is related to the consanguineous parents. Consanguineous parents are the parents who are blood-related.
 

In conclusion, there are many other hypotheses to explain about the causes of Down Syndrome. However, none of which was so far fully convincing. But what we need to aware of is the advancing age of woman. I will recommend you to have your child before 30 years old for woman to avoid from the risk of having Down Syndrome baby.
 

Do you have any knowledge about the cause of Down Syndrome? Share with us.

5 Hypotheses Causing Down Syndrome is a post from: Cytogenetics and Cancer Research

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Down syndrome is a common genetic chromosomal syndrome among the population in the world. It is about 1 in 800 liveborns in the population with Down syndrome. This syndrome starts to be described by a physician named John Langdon Down who published an article in 1866. He stated that there are some children with common characteristics but distinct from other children with mental retardation. He described this syndrome as “Mongoloids”. He used this unfortunate name just because of those children looked like people from Mongolia. The “Mongoloids” was dropped from scientific use since 1960s to stop the ethic insult.

In cytogenetics, about 95% of all patients with Down syndrome have a 47, +21 karyotype. Among these cases there is a small group with familial translocation involving a chromosome 21 and another chromosome with balanced rearrangement. There are some very rare instances of direct transmission of the additional 21 from a Down syndrome mother or father to a Down syndrome child. This is a kind of birth defect syndrome just like Trisomy X and Mosaicism. There are many hypotheses explain how the Down Syndrome occur.

Down syndrome patient looks almost alike to each other. We can simply identify the Down syndrome patient by just looking to their physical outlook. However, a confident clinical diagnosis might be difficult early after birth, especially in prematures. Some of the useful diagnostic signs are brachycephaly (flat-head), small ears, Brushfield spots (brown spots on the periphery of the iris) and low iliac and acetabular index in pelvic radiographs. Congenital malformations are frequent in Down syndrome patients too. Thyroid dysfunction is also significantly associated with Down syndrome and might be the cause for developmental delay. Mentally retardation is the most common feature among the Down syndrome patients.

Generally, female menarche occurs at normal time and pregnancies are common among the Down syndrome patients. However, there is hypogenitalism and hypogonadism among the male patients. Therefore, the male with Down syndrome usually is infertile.

In conclusion, Down syndrome patients need to be taken care as there are various specific problems throughout their life. I will write more about the guideline for optimal medical care on these Down syndrome patients later.

Have you seen any Down syndrome patient? Be patient with them.

Down Syndrome | Birth Defect with Trisomy 21 is a post from: Cytogenetics and Cancer Research

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Since in secondary school, I start burn with curiosity on this description, SUPERWOMAN. Why a female with 47, XXX karyotype can be described as a ‘superwoman’ in Cytogenetics? Is she possesses any super power or advantage just like X-Men?

According to some Cytogenetics studies, females with a 47, XXX karyotype rarely show any physical abnormalities. Therefore, this syndrome is the least frequently detected chromosome aberration in Cytogenetics where that patient possesses one extra X chromosome. They are very soft and gentle than any other normal females in attitude and behavior. That’s why they are acknowledged as ‘superwoman’. Most of them lead to normal lives.

Can the superwomen get their pregnancy? Yes! Gonadal function is normal in majority patients, however, premature ovarian failure might occur too. They usually produce normal children, though there may be a slightly increased risk of non-disjunction occurred among them, which lead to birth of children with other abnormalities such as Down syndrome and Patau syndrome in Cytogenetics.

Frequently, a decrease in intelligence occurs, though it is not sufficiently severe to be classified as retardation. However, there are significant delay in motor and mental development including language and cognitive abilities. They also tend to have behavior disturbances and difficulties in making social contacts.

How could it be? Similar to most of the trisomy syndrome (the possession of a third chromosome in any type of chromosome which results in abnormalities), the superwoman is caused by the meiotic non-disjunction in Cytogenetics. Why meiotic non-disjunction will occur and how to prevent it? Let us explore about this in next section of Cytogenetics and Cancer Research.

XXX Syndrome (Superwoman) | Birth Defect In Cytogenetics is a post from: Cytogenetics and Cancer Research

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Do you know human may consist more than one chromosomally distinct cell lines in Cytogenetics? Most of us believe that each person will just consist of one unique chromosome set (2n) which is the combination of our father’s sperm and our mother’s ovum. However, there is an abnormality that occurred when a person consists of more than one chromosome set in his body. We called this abnormality as Mosaicism in Cytogeetics.

It was the first ever time I heard about mosaicism last week. I was surprised to be informed that a patient has been diagnosed as normal in the first Cytogenetics test but abnormal in the second Cytogenetics test. After further investigation, the scientists found that the patient’s blood cell is normal but his bone marrow is abnormal. The scientists found out that the patient has two different chromosome cell lines in his body. It’s amazing!!

Since that, I just start to worry whether all part of my body is normal. There are several severity levels of mosaicism. Some low mosaicism even undetectable in Cytogenetics. Mosaicism arises after fertilization (occur when the sperm meets with the ovum) through inaccurate segregation of chromosomes at mitosis. The level of mosaicism depends on the stage of development of the organism when the error in division occurs. The level of abnormal effect could be dependent on the percentage and location of abnormal cells present in the body.

Figure 1: Level of Mosaicism

There are two mechanisms account for errors of segregation:

i.            Non-disjunction

-          The failure of the two chromatids to separate at the centromere at metaphase, causing both chromatids to go to the same daughter cell and leading to one hyperdiploid cell and one hypodiploid cell.

ii.            Anaphase lag

-          The loss of a chromatid at anaphase because it is not attached to the spindle and so does not get to the pole. This causes one hypodiploid cell, though the other daughter cell of the pair can be normal.

Figure 2: Segregation Errors At Mitosis

Mosaicism might cause minor abnormality or cause severe disorder. The scientists told me that sometimes the patient‘s parent will found it unacceptable to know that their son had been diagnosed as abnormal in the second test. They might claim that there was error occurred during the Cytogenetics test. The scientists sympathize to them but nothing can do except giving the condolence to them.

The chromosomal abnormalities are the things that we cannot deal with since we cannot change the chromosome inside our body. What we can do is to prevent it from occur. How to do that? Just look forward to my coming post in Cytogenetics and Cancer Research.

Mosaicism (2 In 1 Human) | Birth Defect In Cytogenetics is a post from: Cytogenetics and Cancer Research

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• Transmit the genetic information from cell to cell and from generation to generation.
• Control cellular function and development.

How human chromosomes look like in Cytogenetics?

Figure 1: Normal Chromosome Set (2n)

In the study of Cytogenetics, recognition of different types of chromosomes is very important. Human contains 22 pairs of autosomal chromosomes and a pair of sex chromosomes. Total are 46 chromosomes. Sex chromosomes include chromosome X and chromosome Y. Normal male has 46, XY chromosomes and normal female has 46, XX chromosomes which is shown in the Figure 1.

As we can see, there are different lengths between the chromosomes. The structure of chromosome can be divided to four parts: p arm, q arm, centromere and telomere. Figure 2 is the example of the structurally distinct between the chromosomes.

Figure 2: Structure of Chromosome

From figure 2, the chromosomes can be categorized into 3 types according to the position of the centromere on that chromosome: metacentric chromosome, submetacentric chromosome, and acrocentric chromosome.

Only sex chromosomes differentiate us from male to female. The rest are same for both sexes. It is important to maintain this number of chromosome for us to be a normal human. If anyone deviates from 46, XX or 46, XY, he can be considered as abnormal. Most probably it will cause that person to death. Human cannot have extra chromosome or less chromosome even small part of it.

However, the chromosomal abnormality still occurred among us. The chromosomal abnormality can be either inherited from the parents or occurred spontaneously (de novo) during the zygote is formed. There are many famous chromosomal abnormalities: Down Syndrome, Patau Syndrome, Prader-willi Syndrome, Edward Syndrome, Turner Syndrome and so on. I will talk more about these genetic disorders in coming posts. We will look through deeply on the study of human Cytogenetics and Cancer Research.

What Is Chromosome? Discover Chromosome In Cytogenetics is a post from: Cytogenetics and Cancer Research

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