U1 Chapter 2- Genes and Genetic Diseases

DNA

the genetic master code

Replication

copying of DNA to form an identical daughter molecule

Transcription

genetic message encoded in DNA is transcribed into a complementary strand of RNA

Translation

mRNA produced in transcription is decoded and converted into protein

Progeny

offspring of an organism

Chromosome

structures in the nucleus that contain DNA, which transmits genetic information; each is made of genes in linear order

Gene

DNA, the basic unit of heredity, located at a particular locus on the chromosome

Locus

position each gene occupies along a chromosome

Allele

one of two alternative genes that contain specific inheritable characteristics and occupy corresponding positions on paired chromosomes

Homozygous

a trait of an organism produced by identical or nearly identical alleles

Heterozygous

possessing different alleles at a given chromosomal location

Karyotype/Karyogamy

display of human chromosomes based on length and location of their centromeres

Genotype

the basic combination of genes of an organism

Phenotype

the expression of the gene or individual trait- physical appearance

Carrier

an individual who has a gene for disease but is phenotypically normal

Dominant Trait

traits for which one of a pair of alleles is necessary for expression

Recessive Trait

traits for which two alleles of a pair are necessary for expression

Pedigree Chart

a schematic method of classifying genetic data

Penetrance

the percentage of individuals with specific genotype who exhibit the expected phenotype

Expressivity

the extent of variation in a phenotype of a particular genotype

Genetic Imprinting

different expression of a disease gene depending on which parent transmits the gene

Single-gene Disorders

known to be caused by mutation of a single gene

Multifactorial Disorders

result from small variations in genes combined with environmental factors to produce serious defects

Somatic Cells

have 2 sets of chromosomes and are diploid (double) or 2N

Gametes

have a single set of chromosomes and are haploid (single) or N

Euploid

a cell with an exact multiple of haploid number

Aneuploidy

chromosome complement that is abnormal in number but is not an exact number of N

Disjunction

the normal separation and migration of chromosomes during cell division

Nondisjunction

failure of proper separation and migration of chromosomes during cell division

Deletions

loss of a portion of the chromosome

Duplication

repeated gene or gene sequences

Inversion

a reversal of gene order

Translocation

transfer of part of one chromosome to a non-homologous chromosome

Down Syndrome

Trisomy of Chromosome 21, with an incidence of 1 per 800 live births

Turner Syndrome

Monosomy of X Chromosome, found only in females

Klinefelter Syndrome

XXY Condition, where males have a male appearance but usually sterile

Mental Impairment in Klinefelter Syndrome

Moderate degree of mental impairment associated with Klinefelter Syndrome.

Single Gene Disorders

Inherited genes can be on one or both chromosomes, with inheritance patterns determined by whether the gene is on an autosome or the X chromosome, and whether the gene is dominant or recessive.

Inheritance Patterns

Four basic patterns of inheritance include autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive.

Autosomal Dominant Inheritance

Abnormal allele is dominant and the normal is recessive; phenotype is expressed in either the homozygous or heterozygous state.

Characteristics of Autosomal Dominant Inheritance

Affected person has affected parent; affected person mating with unaffected person have affected and unaffected offspring in equal proportion; males and females are equally affected.

Autosomal Recessive Inheritance

Abnormal allele is recessive; trait must be homozygous for trait to be expressed.

Dominance in Autosomal Recessive Inheritance

Dominant or normal allele masks recessive trait; heterozygous individuals are often phenotypically normal.

Expression of Autosomal Recessive Trait

Trait is only expressed when both alleles are homozygous.

Characteristics of Autosomal Recessive Inheritance

Trait usually expressed in siblings, not in parents; males and females are equally likely to be affected.

Recurrence Risk in Autosomal Recessive Inheritance

For parents of one affected child, the risk of recurrence in subsequent births is 1 in 4.

Carrier Parents in Autosomal Recessive Inheritance

Both parents of an affected child carry the recessive allele; parents of an affected child may be blood relatives.

First cousins

Two sec chromosomes are XX and in the male XY.

Ovum

Contains X chromosomes.

Sperm

Contains X or Y chromosome.

XX offspring

If ovum is fertilized with sperm containing X chromosome; offspring will be XX (female).

XY offspring

If ovum is fertilized by sperm containing Y chromosome; offspring will be XY (male).

X-linked traits

Are expressed in the male and transmitted from father to all daughters.

Transmission of X-linked traits

Never transmitted to sons.

Female carriers

May not express X-linked traits; abnormal X masked by normal X chromosome.

X-linked dominant disorders

Affected male is transmitted to all daughters and none of the sons.

Affected female in X-linked dominant disorders

May transmit gene to either sex.

X-linked recessive disorders

Recessive gene on the X chromosome of male is not balanced by normal gene; trait is expressed.

Matings involving affected males

May result in affected female.

Transmission of X-linked recessive disorders

Males affected with X-linked recessive disorders transmit gene to all daughters and no sons.

Heterozygous female carriers

Transmits recessive X-linked trait to 50% of sons and daughters.

Principles of X-linked recessive inheritance

Males are predominantly affected.

Affected males transmission

Transmit to all daughters and no sons.

Risk for sons of female carriers

Have a 50% risk of being affected.

Risk for daughters of female carriers

Have a 50% risk of being a carrier.

Huntington disease

Best known autosomal disorder; neurological disorder exhibiting progressive dementia and increased uncontrolled movements of the limbs.

Key feature of Huntington disease

Symptoms generally do not manifest themselves until after age 40.

Type 1 neurofibromatosis

Defect mapped to the long arm of chromosome 17; expression is variable.

Cystic fibrosis

Autosomal recessive disease; mapped to long arm of chromosome 7.

Transport of chloride ions

Leads to salt imbalance.

Abnormally thick mucus secretion

Causes digestive organs (especially pancreas) to become blocked, leading to malnutrition.

Lung airway blockage

Makes affected individuals susceptible to bacterial infections.

Duchenne muscular dystrophy

X-linked recessive disorder most predominant in males, characterized by progressive muscle degeneration.

Age of walking impairment in Duchenne muscular dystrophy

Affected people usually can't walk by the age of 10-12.

Heart and respiratory muscle effects

Can affect heart and respiratory muscles, with death usually due to cardiac or respiratory failure.

Average age of death in Duchenne muscular dystrophy

Death often occurs before the age of 20.

Polygenic traits

Traits that result from several genes acting together.

Multifactorial inheritance

Environmental factors influence polygenic expression.

Contribution to trait variation

Both genes and environment contribute to variation in traits.

Familial clustering of multifactorial disorders

Multifactorial disorders tend to cluster in families.

Threshold of liability

Multifactorial disorders are expressed when a threshold of liability has been crossed.

Examples of multifactorial disorders

Pyloric stenosis, cleft lip and palate, neural tube defects, club foot, congenital heart disease, hypertensive heart disease, diabetes mellitus.

Genetic component of diseases

Many human diseases have a genetic component.

Somatic cell DNA content

Each somatic cell has the full complement of DNA, 46 individual chromosomes, organized into functional units called genes.

Function of most genes

Contain the information needed to make functional molecules called proteins.

Gene expression process

The journey from gene to protein consists of two major steps: transcription and translation.

Nucleotides

The building blocks that make up both RNA and DNA, but they have slightly different chemical properties.

Messenger RNA (mRNA)

The type of RNA that contains the information for making a protein, carrying the message from the DNA out of the nucleus into the cytoplasm.

mRNA

Interacts with a specialized complex called a ribosome, which 'reads' the sequence of mRNA nucleotides.

Codon

Each sequence of three nucleotides, usually codes for one particular amino acid.

Transfer RNA (tRNA)

A type of RNA that assembles the protein, one amino acid at a time.

Stop Codon

The signal that protein assembly continues until the ribosome encounters.

Genetic Disorder

A disease caused by a change in the DNA sequence away from the normal sequence.

Genetic Variations

Occur naturally and contribute to the diversity in physical characteristics and disease susceptibility among individuals.

Single Nucleotide Polymorphisms (SNPs)

A form of genetic variation that can occur in the DNA sequence.

Mutations

Changes in the DNA sequence that can lead to the malfunction of genes.

Germline Mutations

Mutations that are inherited.

Somatic Mutations

Mutations that are acquired.

Monogenic Disorders

Genetic diseases caused by mutations in a single gene.

Sickle Cell Anemia

A mutation in the HBB gene leads to abnormal hemoglobin, causing red blood cells to assume a sickle shape and impair blood flow.