Mapping with markers attempts to link chromosomal regions without the need to link alleles. We've discussed linkage mapping previously, which involved mating organisms with different phenotypes, such as flies or plants, to understand the percentage of recombinant phenotypes and thereby comprehend the distance between alleles on the chromosomes. However, this method is impractical for humans due to ethical and practical limitations, making it daunting to effectively study human genetics using traditional breeding approaches. Hence, mapping with molecular markers provides an alternative.
A molecular marker is a DNA segment characterized by an identifiable, unique property, which is polymorphic within populations, meaning it varies between individuals. These markers are incredibly beneficial for pinpointing the locations of unknown genes or alleles, which is challenging with traditional methods that require known phenotypes of specific alleles. Examples include mapping restriction fragment linked polymorphisms (RFLPs). In this process, restriction enzymes are used to cut DNA at sequence-specific sites, which vary among individuals due to mutations or polymorphisms such as single nucleotide polymorphisms (SNPs), deletions, or duplications.
By cutting DNA from various individuals with restriction enzymes and analyzing the resulting fragment lengths on a gel, researchers can track these molecular differences without requiring crossbreeding. RFLPs, thus, generate a type of linkage map based on the variation in DNA fragments rather than direct phenotypic observations. This approach can delineate the genotypes of individuals in a pedigree by analyzing pattern differences in gel electrophoresis results, such as the distinct bands representing homozygous and heterozygous conditions.
Another tool mentioned less frequently is microsatellites, which are repetitive DNA sequences that vary in length and occur periodically across the genome. Techniques like polymerase chain reaction (PCR), Southern blotting, or DNA microarrays can identify these microsatellites' presence and quantify their variability among individuals. Their variance in number and location across the genome serves as markers too, assisting in determining recombination rates and mapping genetic material akin to using recombinant phenotypes in linkage mapping.
In summary, molecular markers facilitate understanding genetic architecture and inheritance patterns by employing DNA sequences directly. This method parallels traditional linkage mapping in utilizing recombination frequencies from natural or experimental matings but does so with molecular rather than phenotypic markers. Mapping with markers harnesses the power of modern genetics, sidestepping the limitations of phenotype-based approaches and expanding our capability to explore genetic landscapes in humans and other organisms.
Let's now proceed with our discussion on more advanced genetic mapping techniques.
