FTM Lecture 11 - Genomics and Human Variation_250202_165100

Course Overview

  • Module: Foundations to Medicine (FTM 11)

  • Lecture Title: Genetic Variation, Genes and Chromosomes

  • Lecturer: Cristofre Martin (cmartin@sgu.edu)

  • Institution: St. George's University

  • Session ID: docmartin

Copyright Information

  • All course materials are subject to copyright and may not be copied, distributed, or published in any form.

  • Year 1 students at St. George’s University may make copies for personal and classroom use only, with unaltered copyright statements.

  • Lecture recordings are for viewing only and cannot be downloaded or copied.

Recommended Reading

  • Textbook: Korf & Irons, Sources of Information 1.1 – OMIM

  • Self-Assessment: Korf & Irons Self-Assessment Review Questions.

Learning Objectives

  1. Describe and compare different types of repetitive DNA, including:

    • Low copy repeats

    • Simple sequence repeats (SSR)

    • Variable number tandem repeats (VNTR)

    • Long interspersed nuclear elements (LINE)

    • Short interspersed nuclear elements (SINE)

    • Pseudogenes

    • Gene families

  2. Differentiate between single nucleotide polymorphisms (SNPs) and rare variants.

  3. Discuss the structure of human chromosomes, including karyotype terminology.

  4. Compare nuclear DNA with organellar DNA (e.g., mitochondrial DNA).

  5. Analyze dosage compensation via X-chromosome inactivation.

  6. Explain epigenetic gene silencing in development, including X-inactivation.

DNA Basics

  • DNA Structure: DNA is organized into genes located on chromosomes within the cell nucleus.

  • DNA structure consists of base pairs forming coding and non-coding regions:

    • Exons: Coding regions transcribed to mRNA.

    • Introns: Non-coding regions removed during mRNA splicing.

    • Regulatory Sequences: Control transcription rates; affected by epigenetic modifications.

Eukaryotic Gene Structure

  • DNA is associated with proteins called histones, forming nucleosomes and higher-order structures.

  • The composition of human DNA includes:

    • Around 3 billion base pairs (haploid) distributed across 23 chromosomes.

    • Approximately 20,000-25,000 unique protein-coding genes.

Types of Genes

  • Unique Single Copy Genes: Code for specific proteins essential for cellular function.

  • Multigene Families:

    • Classic Gene Families: Genes that arose from duplication and maintain high homology (e.g., HOX genes).

    • Gene Superfamilies: Genes with similar functions but lower homology.

Extragenic DNA

  • Accounts for over 98% of the human genome; originally termed “junk DNA.” Its role remains largely unclear, potentially including regulatory functions.

  • Consists of tandem repeated sequences which can be polymorphic and are inherited from both parents.

DNA Variations

  • SNP: A common genetic variant present in more than 1% of the population; about 3 million SNPs exist in humans.

  • SSR: Simple, repeated sequences that can vary in length.

  • VNTR: Longer repeating sequences compared to SSRs; can cause genetic diversity.

  • LCR: Low copy repeat sequences, potentially large and varied in number.

Chromosome Structure and Karyotyping

  • Chromosome Composition: A chromosome is made up of DNA and proteins structured hierarchically:

    • Centromere: Divides the chromosome into p (short) and q (long) arms.

    • Telomeres: Protective ends of chromosomes that are gene-poor.

  • Karyotype: Visualization of chromosomes during metaphase, revealing characteristics such as banding patterns, size differences, and chromosomal abnormalities.

X-Chromosome Inactivation

  • A random process in female embryos where one X-chromosome is inactivated to form a Barr body, regulating gene dosage between genders.

  • XIST Gene: Plays a crucial role in this process by coating and condensing the X-chromosome.

Genetic Disorders and Cataloging

  • Mendelian Inheritance in Man (MIM): A catalog listing genetic traits and variations with unique identifiers (MIM numbers).

    • Used for referencing genetic disorders based on inheritance patterns (autosomal dominant, autosomal recessive, X-linked, and mitochondrial).

Study Points for Students

  • Summarize how DNA functions as the genetic information storage.

  • Analyze the structure of chromosomes and their organizational complexities.

  • Compare and define key genetic concepts: gene, allele, homologous chromosomes, locus, etc.

  • Understand mRNA splicing and alternative splicing's role in protein diversity.

  • Describe the structure and content of the human genome.

  • Discuss types of repetitive DNA sequences, including SSRs and transposable elements.

  • Explore the implications of X-chromosome inactivation and related genetic mosaics.