14. Genetics 3 – Linkage, Crossing Over

Adam Martin introduces the lecture by discussing the genetics of fruit flies, focusing on the white gene mutation that causes white eyes. He explains a cross between red-eyed females and white-eyed males results in all red-eyed F1 progeny. He poses a question about the reciprocal cross involving white-eyed females and red-eyed males, leading to a discussion on sex-linked traits. With audience participation, it's explained that males inherit Y from their father and X from their mother, resulting in white-eyed males and red-eyed females in the F1 generation. This illustrates the concept of sex-linked inheritance, contrasting with Mendel's autosomal trait crosses.

The conversation shifts to recent ALS research at MIT's CAM lab, where a 3D model for ALS, also known as Lou Gehrig's disease, is being developed. This model, which utilizes neurons derived from patients and healthy individuals, aims to find drugs that could potentially cure ALS. Adam Martin connects this to genetics by mentioning a rare X-linked dominant form of ALS, drawing parallels to the sex-linked inheritance discussed earlier. This segment highlights the intersection of genetic research and practical applications in understanding and treating diseases like ALS.

Martin expands on Mendelian inheritance by explaining how crossing individuals that differ in two traits can produce hybrid offspring with heterozygous genes. He introduces the concept of test crosses to reveal the types of gametes produced by F1 individuals. The discussion then moves to Mendel's law of independent assortment, explaining how genes on different chromosomes assort independently, potentially resulting in a 1:1 ratio of parental to non-parental gametes. This section provides a foundational understanding of genetic inheritance patterns and the role of chromosomes in determining traits.

The lecture delves into the concept of linkage, where genes close to each other on a chromosome tend to be inherited together, and crossing over or recombination, where alleles can be exchanged between chromosomes. This segment illustrates how linkage can affect inheritance patterns, with a detailed explanation of how crossing over during meiosis leads to genetic diversity. Martin uses visual aids to clarify the process, emphasizing the significance of linkage and recombination in genetics.

Adam Martin discusses genetic mapping and its origins in the work of Alfred Sturtevant, who utilized linkage concepts to create the first chromosome map. The narrative covers how recombination frequencies between genes can be used to map their positions on chromosomes, offering insights into physical gene mapping. Martin also introduces a practical exercise on constructing a genetic map using a three-point cross, providing an example that illustrates how geneticists determine the distances between genes.

This part of the lecture covers a more detailed application of genetic mapping through a three-point cross, highlighting how to calculate the distances between genes based on recombination frequencies. By analyzing the progeny of a specific cross, Martin explains how to deduce the arrangement of genes on a chromosome and the significance of centimorgans in measuring genetic distance. This segment provides a practical understanding of genetic mapping and its importance in understanding heredity.

Martin offers a comprehensive analysis of recombination data, illustrating how to determine the distances between genes and the concept of centimorgans. He further explains how linkage can cause underestimation of genetic distances due to the possibility of multiple crossovers. This detailed explanation helps clarify the complexities of genetic linkage and recombination, showing how these phenomena contribute to the mapping of genes on chromosomes.

The lecture concludes with a discussion on the linkage of genes to physical structures like the centromere, using yeast genetics as an example. Martin explains how yeast's unique life cycle allows for the observation of meiotic products and the analysis of gene linkage to the centromere. This segment highlights the practical applications of genetic concepts in understanding the physical basis of inheritance and provides an intriguing look into the experimental approaches used in genetics research.