2.4 Genomes & Human Genetics

2.4 Genomes & Genetic Diseases

The Human Genome

• The human genome consists of the complete set of DNA, including all of its genes.

• Example sequences of DNA represented include:

  • ACGTGACTGAGGACCGTG

  • CGACTGAGACTGACTGGGT

  • CTAGCTAGACTACGTTTTA

• Different sequencing technologies allow for deeper insights into genetic compositions and variations.

-OMICS: Advancements in Genome Science

• Genomics: Sequencing of entire genomes.

• Epigenomics: Studying epigenetic elements affecting gene expression.

• Proteomics: Identifying all gene products (proteins).

• Interactomics: Understanding molecular interactions between proteins.

• Metabolomics: Examining the chemical processes involving metabolites.

DNA Sequencing Techniques

• Methods to obtain the nucleotide sequence of genomes.

Sanger Sequencing Method

• Invented by Fred Sanger in 1975.

• Utilizes special nucleotides that prevent DNA polymerase from elongating the DNA chain.

• These nucleotides are known as ddNTPs (dideoxynucleotide triphosphates).

Detailed Sanger Sequencing Steps

• Single-stranded DNA serves as a template.

• Four reaction mixtures prepared with ddATP, ddCTP, ddTTP, and ddGTP.

• Gel electrophoresis used to separate reaction products based on length.

• The sequence can be read from the autoradiograph of the fragments.

Whole Genome Shotgun Sequencing

• Developed by J. Craig Venter.

• Involves cutting genomes randomly into fragments for sequencing.

• Each segment is sequenced, then assembled back with redundancy to form a complete genome.

Next-Generation Sequencing (NGS)

• Fragments are added with adapters, attached to flow cells, and subjected to PCR.

• Efficient for massively parallel sequencing, which dramatically decreases costs.

Decreasing Genome Sequencing Costs

• The cost for whole genome sequencing has significantly decreased from over $100 million to less than $1000 with advancements in technology.

Human Genome Project

• Launched to sequence all human DNA with contributions from various global research centers.

• First draft completed in 2000; full sequence by 2003.

• Goals included identifying every human gene’s sequence and location.

Results of the Human Genome Project

• Approximately 21,000 genes identified with varying functions in 3.2 billion nucleotide pairs.

• 98.5% of DNA does not code for proteins─includes regulatory and noncoding regions.

ENCODE Project

• Launched in 2003 to map all functional elements in the human genome.

• Discovered that 80% of the genome has active elements, contradicting the notion of "junk DNA."

Roadmap Epigenomics Project

• Focuses on genetic switches related to disease, emphasizing the role of epigenetic control.

• Found millions of switches impacting gene expression.

Epigenome Changes and Disease

• Combination of epigenetic changes rather than single modifications is critical in disease emergence.

• Understanding enhancer regions is vital for connection to diseases like cancer.

Project Goals

• The Genome 10K Project aims to sequence the DNA of 10,000 vertebrates.

• The Earth Biogenome Project aims for sequencing all eukaryotic life on Earth, highlighting urgency for preserving genetic diversity.

Chromosome Nondisjunction and Genetic Alterations

• Chromosome number alterations can lead to serious genetic conditions, such as Down syndrome.

• Nondisjunction during meiosis results in gametes with abnormal chromosome numbers.

Examples of Genetic Conditions Due to Nondisjunction

1. Down Syndrome (Trisomy 21)

   • Characterized by an extra copy of chromosome 21.

2. Turner Syndrome (Monosomy X)

   • Affects females, missing an X chromosome.

3. Klinefelter Syndrome (XXY)

   • Males with an extra X chromosome may experience fertility issues.

Autosomal Disorders

• Dominant Disorders:

  • Achondroplasia, Alzheimer's disease, Huntington's disease.

• Recessive Disorders:

  • Albinism, Cystic fibrosis, Sickle-cell disease.

X-Linked Disorders

• Associated with genes that are located on the X chromosome, affecting primarily males due to their XY chromosome pattern.

• Examples include hemophilia and color-blindness.

Sex Determination Complexity

• Various mechanisms determine sex across species, including genetic, environmental, and social factors.

• For example, temperature influences sex in some reptiles.