Lecture 1

Learning outcomes

1. Be familiar with the three general classes of genetic diseases

• Chromosome disorders

  • Caused by excess or deficiency of all/part of a chromosome

  • ~50% of spontaneous abortions; 7 in 100 live births

• Single-gene disorders

  • Due to mutation in 1 or both copies of a single gene

  • ~2% of the population

• Multifactorial disorders with complex inheritance

  • Combined effect of multiple genetic defects, often influenced by environment

  • > 50% of the population

2. Be able to describe the basic features of the nuclear genome (size, approximate number and kinds of genes and chromosomes)

• 6.6 billion base pairs per diploid cell

• 25,000 protein coding genes (mRNA)

• 25,000 noncoding RNA genes

  • tRNAs, rRNAs, snoRNAs, snRNAs, lncRNAs,miRNAs —> Structural, catalytic, or regulatory roles

• 23 pairs of homologous chromosomes

  • Autosomes: 1-22

  • Sex chromosomes x & y

3. Be familiar with the human karyotype and terms used to describe chromosomal loci

• G-banding (Giemsa staining) of metaphase chromosomes reveals banding patterns

  • Can reveal defects in the number or structure of chromosomes

• Metacentric: centromere is located in the middle of chromosome

• Submetacentric: slightly off centered

• Acrocentric: centromere is toward 1 end of chromosome

• Telocentric: centromere is located at the end of chromosome (rare)

4. Be able to describe the relative abundance of single-copy and repetitive DNA sequences in the human genome

• Genome contains equal percentages of single copy and repetitive DNA

  • Single-copy: unique sequence of DNA. includes most genes and regulatory elements. Less than 15% of the genome encodes proteins.

  • Repetitive DNA sequences: satellite DNA and dispersed elements

• Satellite DNA: tandem repeats of relatively short (5-170 bp) sequences

  • Can span extremely large regions of the genome

  • Clustered in specific regions (centromeres, heterochromatin)

  • 10-15% of genome

• Dispersed repeats: repetitive elements that are dispersed through the genome

  • Includes short- and long- interspersed nuclear elements (SINEs [Alu element] and LINEs)

  • 100s-1000s of bp in length

  • 30% of genome

  • Very important because many of these elements are transposons —> lead to mutations

5. Be able to describe the basic features of the mitochondrial genome (size, approximate number and kinds of genes)

• Mitochondrial DNA

  • Multiple circular DNA molecules ~16.6 kb

  • Some genetic diseases are caused by defects in the mitochondrial genome

• Has 38 genes containing:

  • 14 protein coding genes

  • 2 ribosomal RNAs

  • 22 transfer RNAs

Key Terms

Chromosome

Single-gene disorder

Multifactorial disorder with complex inheritance

tRNA

rRNA

snoRNA

snRNA

lncRNA

miRNA

mRNA

Karyotype

G-banding

Autosome

Sex chromosome

Single-copy sequence

Repetitive DNA

Satellite DNA

Dispersed repeats

SINE

LINE