Human chromosome 4 sequencing and stngle nucleotide polymorphism (SNP) analysis of an achondroplasia individual
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Date
2011
Authors
Ling Sze, Lee
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Abstract
Achondroplasia is the most common cause of short-limbed dwarfism in
humans, affecting 250,000 individuals worldwide. This genetic disorder results in
various social and medical complications. The majority of achondroplasia cases is
sporadic and result from de novo mutations. This autosomal-dominant disorder is
caused by single nucleotide mutations in the gene encoding the type 3 receptor for
fibroblast growth factor (FGFR3). Tlus study focused on understanding the genetic
basis of achondroplasia by identifying SNPs from flow-sorted human chromosomes
of an achondroplasia volunteer of Asian origin. Chromosome staining and the
bivariate flow karyotyping of human chromosomes were successfully optimized.
Whole Genome Amplification (WGA) was carried out to generate high-throughput
sequencing data. Thorough analysis of the sequence data and SNPs was unable to
identify any known mutations of achondroplasia and hypochondroplasia. Thus, it
indicates that the classical achondroplasia indicator gene,fgfr3, may not be the only
indicator in this particular case.
Why am I different?
Living as a shorter person in a world that's designed for the tall people- Why
am I different?- is the most frequently asked question I always have.
I look different. Everywhere I go, I attract curiosity and I get stared at a lot. As
far as I know, I have what I think is an ordinary life. I live with my parents and two
sisters. I do not notice the little things that I have to do differently from other people.
I felt that I am a normal person, living a normal life. I eat, sleep, breathe, study and
get ill, just like everyone else. But why am I still different?
I know that some little people like me have a lot of health problems. Personally,
I have walking problems and get more back and joint pain than others my age but
this certainly is not enough to stop me to go for sports or activities that I enjoy. Thus,
I want to change the lifestyle of a little person, who have more serious health
problems than I do, to enable them to lead a normal life like other people.
As Nobel laureate Paul Berg of Stanford University mentioned before ''All
human disease is genetic in origin." So, ho\V do I investigate the mystery c f the genes
that made me different and find the answer to my question?
Since the completion of the Human Genome Project, the sequence of the
human genome is providing the complete view of the genetic heritage. The human
genome, the complete set of human genes, comes in 23 separate pairs of
chromosomes. If a human genome is a book, then every human being has a story to
tell. Each book comes in 23 chapters, which are called chromosomes. Each chapter
contains stories, called genes. Here, I will be telling you the story of one of the
chapters in my book, chromosome 4, and focusing one of the stories, the fgfr3 gene
that is related to a one of the best-known genetic diseases, Achondroplasia.
Single-nucleotide polymorphisms (SNPs) are one-base variations m DNA
sequence. Each person's genetic material contains a unique SNP pattern that is made
up of many different genetic variations. Most SNPs are not responsible for a disease
state. Instead, they can often be helpful when trying to find genes responsible for
inherited diseases and serve as biological markers for pinpointing a disease on the
human genome map. Occasionally, a SNP may actually cause a disease. Therefore, it
can be used to search for and isolate the disease-causing gene.
Achondroplasia has been mapped to the tip of the short arm of chromosome 4.
So, how can we better understand this genetic disorder? There are two possible ways:
1. Sequence a full human genome and analyze the presence of SNPs, or
2. Study chromosome 4 in-depth and compare the SNP patterns between
individuals affected by achondroplasia and individuals unaffected by the
genetic disorder.
At the moment, since achondroplasia-associated mutations are already known
to be located in chromosome 4, I will first study specifically chromosome 4 to
identify SNPs that could be related to the achondroplasia disease family. Now, how
can I identify and isolate chromosome 4 from the 23 pairs of chromosomes? One
possible way is to use a rapidly developing technique in research and clinical practice,
the flow cytometry and sorting instrument. The flovv cytometry technique enables us
to isolate the desired chromosome from the other chromosomes. Directly after
isolation, the flow-sorted chromosomes can be sequenced to determine the nucleotide
sequence. As human DNA sequences are 99.9% identical to each other, the 0.1% of
variation can provide many clues to many diseases and common illnesses. The
identification of such variations can help explore the mystery of achondroplasia.
Description
Keywords
Chromosome , Nucleotide polymorphism