Biomedical Engineering Reference
In-Depth Information
The genome is also fi lled with many regulatory sequences, usually found
preceding the actual unique gene sequence that is transcribed into mRNA.
Two of these are: (i) The CCAAT box sequence, which is at the 5' beginning
of the gene and is usually 70-90 bases upstream from the starting sequence
for gene transcription. This area binds important protein factors that are
needed to initiate transcription of the gene into mRNA, and (ii) the TATA
box sequence, which is generally 20-30 bases from the starting point for
transcription. This area is also important in binding initiating factors for
gene transcription.
The unique gene sequences themselves can also be identifi ed by several
important features that are used for gene identifi cation in the vast amount
of non-coding DNA. The term open reading frame is often used to indicate
a DNA region that starts a gene, and they start with the universal triplet
ATG that is the starting point for gene transcription. The exon contains the
informational sequence that codes for an amino acid sequence. In humans,
most genes have many exon sequences that are interrupted with stretches
of non-coding DNA sequences called introns. In most instances, the introns
will start with GT bases and end with AG bases. These bases are recogni-
tion sites that will serve as markers for the enzyme system that splices these
introns out of the processed mRNA. The splicing of exons from introns has
been a source of study and amazement, since it presents a way for the gene's
information to be reshuffl ed in many ways, which is called alternate splic-
ing. This process permits many more proteins to originate from one gene
sequence.
Gene sequences also have unique terminating sequences called termi-
nation codons that signal the end of transcription at the 3' end of the gene.
These codons are TAA, TAG, and TGA. Also, both the telomeres and cen-
tromeres of all human chromosomes have unique repeated sequences that
can mark them both molecularly and cytogenetically.
7.8 Copy number variations (CNVs)
Early on in the investigation of the genome it became apparent that indi-
viduals had variations in the numbers of a specifi c repeated sequence and
that these variations were useful in identifi cation, and could even be used
in forensic investigations to determine if a crime suspect actually was at
the site of the crime. These
variable numbers of tandem repeats
(VNTRs)
are characterized by short sequences arranged in a head-to-tail fashion and
repeated multiple times in a tandem array. Labeled probes can easily be
made for these VNTRs and their numbers can be counted in a simple gel
electrophoresis procedure. The VNTRs are inherited in a Mendelian fash-
ion, hence identical twins, having inherited the same chromosome pair from
each parent, would have identical electrophoresis patterns for their VNTRs.
