Clinical Genetics
Introduction
Genetics:
Has comes to occupy a pivotal position in the entire subject of modern biology. For any life
activity that involved human, plant, animal, or microbial life, an understanding of genetics is thus
essential.
Genetics like no other scientific discipline, has become central to numerous aspects of human
affairs. It touches our humanity in many different ways. Indeed, genetic issues seem to surface
daily in our lives, and no thinking person can afford to be ignorant of its discoveries.
Medical research is revealing more and more genetic predispositions to serious conditions, as
well as to milder ailments. A large portion of human ill health has a genetic basis. For example,
it has been estimated that at least 30 percent of pediatric hospital admissions have a direct
genetic component.
Clinical Genetics:
Is the specialty concerned with the diagnosis of inherited disorders and birth defects, with the
estimation of genetic risks and with genetic counseling of family members. Clinical geneticists
generally work in multidisciplinary regional genetic centres, along with scientists, clinical coworkers (genetic associates and nurses) and academic colleagues.
The specialty of Clinical Genetics is constantly changing and the clinical geneticist must be able
to take account of new findings and alter practice accordingly. He will also need to act as an
information resource for other medical specialties. Clinical geneticists need a wide range of
clinical skills since genetic disorders can affect people of all ages and all body systems.
1
Communication skills are particularly important in transmitting complex concepts and test
results to families to enable them to choose an appropriate course of action.
Genetic ill health has many facets. Many inherited genetic diseases (such as cystic fibrosis,
phenylketonuria, and muscular dystrophy) are caused by abnormal forms, mutations, of single
genes inherited through the gametes (sperm and egg). The positions of the single genes that
cause some of the better-known hereditary disorders. Many of the genes these genes have been
isolated and analyzed at the molecular level.
For example, abnormal forms of genes BRCA1 and BRCA2 together account for two-thirds of the
cases of familial breast cancer. BRCA1 is also associated with predisposition to ovarian cancer.
BRCA1 codes for a protein that likely function to regulate the activity of other genes. In both
these cases, understanding how genes cause the rarer familial forms of the disease will also
undoubtedly lead to an understanding of and effective therapy for the more common "sporadic"
forms of the diseases and here come the role of medical genetics.
Medical genetics deal also with another type of genetic illness that caused by chromosomal
anomalies, abnormalities of chromosomal structure or number. A familiar example is Down
syndrome, caused by possession of an extra copy of one specific chromosome (chromosome 21).
The clinical geneticist
1. Cytogenetics.
2. Biochemical genetic.
3. Molecular genetic.
2
Clinical geneticists should also play their part in public education and public debate about social
issues arising from the applications of human genetics, and are expected to provide appropriate
advice to professional colleagues.
Conclusion:
Medical genetics is one of the most rapidly advancing fields of medicine, and molecular genetics
is now integral to all aspects of biomedical science. Medical genetics provides a unique
perspective on function of the human body in health and disease; it is both a clinical specialty
and a basic science. Every physician who practices in the 21st century must have an in-depth
knowledge of the principles of human genetics and their application to a wide variety of clinical
problems, and each medical school must find the best way to incorporate genetics teaching into
its own curriculum.
3
The Structure of Human Chromosomes
Nomenclature
Chromosomes are named so because of their ability to take up certain stains, as in Greek
"chromos" means color and "soma" means body. The genome of a human diploid cell contains
3x109 nucleotide pairs arranged in 46 chromosomes, 22 pairs of autosomes numbered 1-22 and
the sex chromosomes which are referred to as X and Y (Tjio & Levan, 1956). The centromere
divides each chromosome into a short (p) and a long (q) arm. Chromosomes are classified
according to their size, the location of the centromere, and the banding pattern along each arm,
which is a unique pattern of light and dark transverse bands that are numbered from the
centromere outward (Figures 1-4).
Human chromosome anatomy
4
Classification of human chromosome according to the position of centromer
Chromosomal aberrations are only detectable when alterations involve large parts of the genome,
more than approximately 4 million base pairs (0.13% of the genome). If we consider the distance
between London and New York equal to the length of the haploid human DNA, then 4 million
base would be equivalent to 8 km. Chromosomal aberrations observed in neoplastic cells are of
two main types; numerical changes, i.e., gain or loss of whole chromosomes, and structural
aberrations, which may be balanced (no resulting loss or gain of genetic material), or unbalanced
(with loss or gain of genetic material) (Table 1). According to the biological significant they can
also be classified into:
Primary changes
 Essential in establishing the neoplasm
 Frequently found as the sole anomaly
 Usually specific for a certain type of tumors
5
Secondary changes

Arise in cells already caring the primary changes
 Usually the are nonrandom
 Important in the progression of the disease.
Chromosome 8
Band p23
3
2 2
Short arm (p)
1
1
Centromer
2
1
1
1
2
3
1
Region q2
2
Long arm (q)
2
3
4
6
Table 1 Abbreviations and descriptions of the most common
chromosome abnormalities
Rearrangement
Abbreviation Description
Addition
Add
Addition of unknown material to a chromosome
Deletion
Del
Interstitial or terminal loss of chromosomal material
Derivative
Der
Double minute
Duplication
dmin
Dup
Insertion
Ins
Inversion
Inv
Structurally rearranged chromosome resulting from more than
one change within a single, two, or even more chromosomes
Multiple copies of acentric chromosomal material
Duplication of chromosomal segment
A chromosomal segment has moved into an interstitial position
within the same or another chromosome
A chromosomal segment has rotated 180 degrees
Isochromosome I
Mirror image chromosome with two identical arms
Marker
Mar
Rearranged chromosome in which no part can be identified
Monosomy
Translocation
Ring
Trisomy
T
R
+
Loss of one chromosome copy
Transfer of material between two or more chromosomes
Break and fusion of the two chromosome arms
Gain of one chromosome copy
7
Loss
Numerical changes
 Gain or loss of whole chromosomes
Gain
Numerical changes
Loss
Structural changes
 Balanced - no loss or gain of genetic
material
 Unbalanced - loss or gain of genetic
Gain
material
Structural changes
8
3
2
1
1
2
3
4
2
1
1
2
1
1
2
3
6
5
4
3
2
1
2
1
3
2
1
1
2
1
2
3
4
5
1
2
1
2
3
4
5
4
3
2
1
2
1
1
2
3
4
5
6
1
2
3
4
5
6
7
3
2
1
1
2
3
4
1
2
1
2
3
4
3
2
1
1
2
1 3
1
1
6
13
19
2
1
1
2
3
2
1
1
2
5
4
3
2
1
6
5
4
3
2
1
1
2
3
4
1
2
3
4
1
2
3
4
5
6
2
7
14
7
2
1
5
4
3
2
1
1
1
2
1
2
3
4
5
6
3
2
1
1
2
3
1
2
3
4
1
2
3
2
1
1
3
2
3
1
1
2
3
1
1
20
1
1
2
2
1
1
2
2
1
1
2
1
1
2
3
2
1
1
1
2
6
5
4
3
2
1
4
3
2
1
1
2
3
1
2
3
4
5
6
7
8
9
3
2
1
2
1
1
2
3
2
1
1
4
3
2
1
3
2
1
1
3
1
1
5
4
3
2
1
1
1
2
3
4
5
2
1
2
3
6
9
3
1 2
1
10
16
1
1
2
1
1
2
3
1
1
2
3
2
1
1
2
1
2
3
4
5
6
1
5
4
3
2
1
1
5
2
3
4
5
3
2
1
1
2
3
4
5
3
2
1
5
12
Y
18
1
2
3
4
5
1
2
3
4
1
1
2
1
2
3
11
1
1
2
2
1
1
2
1
1
3
2
1
4
3
2
1
1
2
4
3
1
2
3
4
5
6
7
8
1
2
3
4
5
5
4
3
2
1
1
2
3
4
11
X
17
1
2
3
4
5
2
1
1
1
1
2
3
2
1
2
3
4
5
1
3
2
1
2
3
2
1
4
1
1 2
3
1
2
3
2
1
1
22
4
2
2
3
3
2
1
8
1
2
3
4
3
2
1
1
2
3
4
5
1
2
3
4
5
6
15
21
6
7
8
9
Figure 1.2 NormalG-banded human male karyotype
10