What is Genetic Analysis?

Genetic analysis refers to the process of studying and analyzing changes in chromosomes or genes using different methods in scientific fields such as genetics and molecular biology. It involves the localization and identification of genes and the detection of inherited or genetic disorders caused by mutations or other abnormal variations in our genome.

The importance of genetic analysis

Various practical advancements in genetics and molecular biology have resulted from genetic tests. Through the identification of copy number variations and mutations, genetic testing is used to identify genetic or hereditary problems and to make a clinical diagnosis of specific diseases such as cancer. By determining which genes are faulty, genetic testing is employed in the diagnosis and treatment of malignancies. 

Genetic testing can provide essential information for the diagnosis, treatment, and prevention of disease. Variations in genetic material that may raise the risk of disease or impact treatment responses can be detected by genetic tests. Understanding the organization of genes on chromosomes is facilitated by genetic linkage studies. Single nucleotide polymorphisms (SNPs) and mutations are detected using several genetic testing techniques. A huge number of SNPs on the genomic sequence are examined using whole-genome scanning. We can compare the patterns of normal and diseased patient samples to find the SNPs that could be responsible for a specific disease.

Types of genetic testing

Cytogenetics (Chromosome studies)

The study of morphology and the number of chromosomes is referred to as cytogenetics. In deoxyribonucleic acid (DNA), genes are located on chromosomes. Each chromosome will have a characteristic banding pattern (transverse darker or lighter regions) of its own. Based on such patterns, different chromosomes are identified. Chromosome bands are made clear by cytological staining techniques, called banding techniques. The stained chromosomes glow in alternate dark and light bands when viewed under ultraviolet light. Staining is done with specific fluorescent dyes (fluorochromes) by subjecting the chromosomes to specific biochemical treatment. Chromosome banding methods are used for the elucidation of the structural details of chromosomes for their identification. A blood sample, a prenatal specimen, or other tissue sample are commonly used for chromosome analysis.

Biochemical genetic tests

Biochemical genetic testing involves the study of enzymes whose abnormal conditions lead to defects. Enzymes control chemical reactions in our bodies. The enzymes may be absent or deficient or have altered activity, which can result in malformations such as congenital malformations. It aids in the study of the mutations in genes responsible for the enzyme defect. Depending on the type of disorder, this study may use blood, spinal fluid, urine, or other tissue samples.

DNA studies

To detect abnormalities in the genetic code and study genes, DNA analysis methods are used. For these studies, two ways of analysis are used: direct and indirect DNA studies. In the former, the analysis uses methods such as polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH). This type of analysis detects abnormalities including duplication, deletion, point mutation, or trinucleotide repeats. For direct analysis, DNA is obtained from a blood sample. The latter involves pedigree analysis, linkage studies, etc. For this analysis, a sample of blood from a close family member (proband, his parents, siblings) is used. Linkage studies involve the analysis of families who have multiple family members with diseases such as cancer.

Different methods of genetic testing

Genetic analyses use molecular methods such as DNA sequencing, DNA microarrays, and PCR, and cytogenetic methods such as FISH, karyotyping, and DNA studies such as pedigree analysis and linkage studies.

Karyotyping

The chromosomal characteristics of a cell or an individual are known as the karyotype. It signifies the number, size, kind, shape, structure, and other characteristics of the chromosomes of a given species.

A somatic human cell has only 46 chromosomes, namely 44 autosomes (A) and two sex chromosomes. The sex chromosomes include two X-chromosomes in females (XX), and one X-chromosome, and one Y-chromosome in males (XY). Thus, the normal karyotype of a human female and male is 44A + XX and 44A + XY, respectively. Karyotyping is used to detect genetic abnormalities, abnormal structures or numbers of chromosomes, mutations, and evolutionary changes in the past by observing chromosome banding patterns.

Fluorescence in situ hybridization (FISH)

FISH is a cytogenetic method invented by Gall and Pardue, and multicolor FISH was experimentally demonstrated by Christoph Lengauer for detecting and localizing particular DNA sequences on chromosomes. It makes use of probes (tagged nucleic acid sequences) to visualize specific DNA or ribonucleic acid (RNA) sequences on mitotic chromosome preparations. This approach is beneficial for mapping genes and detecting chromosomal abnormalities. FISH is frequently employed in genetic testing, medical science, and species identification to discover specific DNA functions. It can also be used to detect and monitor cancer cells in circulation.

Gene mapping

Genetic mapping (linkage mapping, crossover mapping, or chromosome mapping) is the graphic representation of the linear sequence of the non-allelic genes of a linkage group on a chromosome. It reveals the relative locations of the genes on a chromosome and also the relative genetic distance between them. Gene mapping is done by determining the number of crossovers between the linked genes. So, it is also called crossover mapping. 

Polymerase chain reaction (PCR)

PCR is known as a technique for rapidly creating copies of a particular DNA sample in billions, permitting the amplification of a small amount of DNA or a portion of it to a large amount to investigate in depth. Many processes used in genetic testing and research, including infectious agent identification, DNA cloning, DNA-based phylogeny and functional analysis of genes, and paternity testing, rely on it. Using the PCR amplification technique, copies of very small amounts of DNA sequences are efficiently increased by a chain of temperature changes in different steps.

DNA sequencing

DNA sequencing is an essential method used in genetic testing. This technique helps to determine the order of nucleotide bases (adenine, thymine, cytosine, and guanine) in the genome. By determining the patterns, it helps to study genetic traits and behaviors.

Pedigree analysis

A pedigree is the ancestral history or genealogy of an individual or a family group used in genetics. It is the systematic representation of a family tree that provides useful data about the genetic background of individuals. Pedigree analysis is the study of the history of the inheritance, distribution, and expression of a gene or a genetic trait in different generations of a lineage. In practice, it involves the construction of a family tree based on the phenotypic record of the family over several generations. In genetics, it is significant in the study of some human traits and genetic disorders.

The pedigree analysis involves two major steps, namely (i) the preparation of a pedigree diagram or pedigree chart, and (ii) interpretation of the data provided by the pedigree chart and the formulation of conclusions and predictions. Pedigree diagrams are often used in human genetics for the analysis of Mendelian inheritance. For preparing a pedigree chart, the information about the history of the transmission and expression of a specific trait in a lineage is collected first. Then, using symbols, the different generations in which the trait under study is expressed are plotted on the family tree.

Context and Applications

This topic is significant in the exams at school, graduate, and post-graduate levels, especially for bachelors in zoology/botany/biomedical genetics/human genetics and masters in zoology/botany/biomedical genetics/human genetics.

Practice Problems

Question 1: In genetics, ______ is used for the study of the history of the inheritance, distribution, and expression of a gene or a genetic trait in the different generations of a lineage.

1. Microarray
2. Pedigree analysis
3. DNA sequencing
4. None of the above

Answer: Option 2 is correct.

Explanation: Pedigree is the systematic representation of a family tree that provides useful information about the genetic background of individuals.

Question 2: Which of the following methods is included in genetic tests?

1. DNA microarray
2. DNA sequencing
3. PCR 
4. All of the above

Answer: Option 4 is correct.

Explanation: DNA microarray, DNA sequencing, and PCR are the methods used for genetic testing. The microarray is used for detecting the expression of a large number of genes simultaneously. DNA sequencing helps to determine the order of nucleotides. PCR helps to amplify a piece of DNA into thousands or millions of copies.

Question 3: Which technique helps to determine the order of nucleotide bases in the genome?

1. DNA microarray
2. DNA sequencing
3. PCR
4. None of the above

Answer: Option 2 is correct.

Explanation: DNA sequencing is the technique that helps to determine the order of nucleotide bases (adenine, thymine, cytosine, and guanine) in the genome.

Question 4: Which of the following is an application of PCR?

1. Diagnosis and detection of hereditary
2. Cloning of DNA
3. Functional analysis of genes.
4. All of the above

Answer: Option 4 is correct.

Explanation: Applications of PCR include diagnosis and detection of hereditary and infectious diseases, DNA cloning, DNA-based phylogeny, and functional analysis of genes. So, all of the options given are PCR applications.

Question 5: Indirect DNA studies involve ______.

1. PCR or FISH
2. Linkage studies or pedigree analysis
3. Both 1 and 2
4. None of the above

Answer: Option 2 is correct.

Explanation: Indirect DNA studies involve the analysis of families who have multiple family members with diseases such as cancer. Pedigree analysis, linkage studies, etc. are used for this type of study.