Discovering Human Genes & Cystic Fibrosis

Flashcards reviewing key vocabulary and concepts from a lecture on human genes, disease classification, and Cystic Fibrosis.

Gene

A stretch of DNA whose sequence determines the structure and function of a specific functional molecule (usually a protein).

Codon

A series of 3 base pairs

Transcription

The process of creating RNA from DNA.

Translation

The process of creating protein from mRNA.

Gene

A length of DNA that contains instructions for making a specific protein.

23 pairs of chromosomes

Genes are arranged along these in the cell nucleus

Amino acid sequence

Genes work by specifying this of a protein.

Law of Segregation

A normal (somatic) cell has two variants (alleles) for a Mendelian trait; a gamete (sperm, egg, pollen, ovule) contains one allele, randomly chosen from the two somatic alleles.

Genetics

Understanding the origin and expression of individual human uniqueness.

Genomics

Identifying and characterizing genes and their arrangement in chromosomes.

Bioinformatics

The use of computer algorithms and computer databases to study genes, genomes, and proteins.

Four categories of disease

Monogenic, complex, genomic, and environmental.

Disease databases

OMIM and locus-specific databases

Four approaches to identifying disease genes

Linkage, GWAS, chromosome analysis, and sequencing

Monogenic disorder

Caused primarily by mutation(s) in a single gene.

Autosomal dominant (AD) inheritance

Males and females are affected; male to male transmission; recurrence risk is 50%.

Autosomal recessive (AR) inheritance

Males and females are affected; recurrence is within a sibship; recurrence risk is 25%.

X-linked recessive

Males are affected and are related through their mothers; females are unaffected, or mildly affected, depending on X-inactivation; recurrence risk is 25%.

Cystic Fibrosis

Is a heterogeneous recessive genetic disorder, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 70% cases.

Classic cystic fibrosis characteristics

Chronic bacterial infection of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to obstructive azoospermia, and elevated concentrations of chloride in sweat.

Apical

The CF transmembrane conductance regulator (CFTR) gene encodes a protein expressed in this membrane of exocrine epithelial cells.

Region q31.2 on the long (q) arm

CFTR is found here on human chromosome 7.

CFTR Protein normal function

a chloride channel protein found in membranes of cells that line passageways of the lungs, liver, pancreas, intestines, reproductive tract, and skin

Chloride

CFTR controls this ion movement in and out of the cell.

CFTR five domains

Two membrane-spanning domains (MSD1 and MSD2), two nucleotide-binding domains (NBD1 and NBD2), and a regulatory (R) domain.

Delta F508

The most common CF-causing mutation, occurs in the DNA sequence that codes for the first nucleotide-binding domain (NBD1).

Sweat test

Gold Standard

Complex disorders

Multiple genes are involved; complex diseases are non-Mendelian; they show familial aggregation, but not segregation.

Genomic (chromosomal) disorders

Many diseases are caused by deletions, duplications, or rearrangements of chromosomal DNA; aneuploidy can occur.

Environmental impact

Genes affect susceptibility to environmental insults, and infectious disease.

Four approaches to identifying disease genes

Linkage analysis, genome-wide association studies (GWAS), identification of chromosomal abnormalities, and genomic DNA sequencing.

Linkage

Refers to two genes which are transmitted together from one generation to next; recombination fails to separate linked genes.

Genomic microarrays

A microarray technology that detects chromosomal abnormalities