Genes and Human Development

Genes and Human Development

• Genes, which are segments of DNA, are the "recipes" or blueprints for protein synthesis
• Gene expression can be regulated by other genes
• Genetics is the study of the mechanism of heredity
• Mendel proposed the basic principles of genetics in the mid-1800s
• He focused on inherited characteristics as either dominant or recessive
• Human traits are more complex than simple dominant/recessive inheritance
• The Human Genome Project determined the human DNA sequence
• This aids in genetic research and genetic screening

Genetics Vocabulary

• The diploid number of chromosomes is 46 in all cells, except gametes
• Gametes are sperm and egg cells
• Chromosomes exist in 23 pairs of homologous chromosomes
• One pair determines genetic sex: XX for female, XY for male
• The other 22 pairs are autosomes that guide the expression of most traits
• A karyotype displays the diploid chromosomal complement in homologous pairs
• A genome is the genetic (DNA) makeup
• It consists of two sets of genetic instructions, one maternal and one paternal

Gene Pairs (Alleles) Terms

• Alleles are genes at the same locus (location) on homologous chromosomes
• The DNA sequence of alleles can be the same or different
• Homozygous alleles are the same for a single trait
• The DNA sequence is the same on both homologous chromosomes
• Heterozygous alleles are different for a single trait
• The DNA sequence is different on each homologous chromosome
• Dominance occurs when one allele masks or suppresses the expression of its recessive partner
• Dominant alleles are denoted by a capital letter, while recessive alleles are lowercase
• Example: loose thumb ligaments are dominant (J), tight thumb ligaments are recessive (j)
• A dominant trait is expressed even if the other allele codes for a recessive trait
• For example, JJ or Jj results in double-jointed thumbs
• A recessive trait is expressed only if both alleles are recessive
• For example, tight thumb ligaments occur only if the person has jj

Genotype and Phenotype

• Genotype is the genetic makeup of a person for a trait
• For double-jointed thumbs, there are three possible genotypes: JJ, Jj, jj
• Phenotype is the physical expression of the genotype
• For double-jointed thumbs:
• JJ or Jj genotypes result in double-jointed thumbs, because J is dominant
• The jj genotype will not result in double-jointed thumbs

Genetic Variation

• Genetic uniqueness results from three events:
• Segregation and independent assortment of chromosomes
• Crossover of homologues
• Random fertilization of eggs by sperm

Chromosome Segregation and Independent Assortment

• Two important separations of traits occur in meiosis I of gametogenesis:
• Segregation refers to the separation and distribution of two alleles for a particular trait into two different daughter cells
• For the pair Jj, allele J will go into one daughter cell, and allele j will go into the other
• Errors in segregation can cause cancer, infertility, and Down syndrome
• Independent assortment refers to the distribution of alleles for two different traits on two different chromosomes independently of each other
• For example, if Bb is on one chromosome and Jj is on another, possible inheritance combinations are BJ, Bj, bJ, and bj

Crossover of Homologues and Gene Recombination

• Genes on the same chromosome are linked and passed to daughter cells as a unit
• During crossover (chiasma), homologous chromosomes can break and exchange gene segments:
• This results in recombinant chromosomes
• Chromosomes become a mixture of contributions from each parent
• Crossover results in tremendous variability

Random Fertilization

• A single egg is fertilized by a single sperm in a random manner
• Genetic variation implies the odds of you being who you are are greater than 1 in 72,000,000,000

Dominant-Recessive Inheritance

• Inheritance involves interactions between dominant and recessive alleles
• A Punnett square predicts the possible gene combinations from the mating of parents with known genotypes
• For albinism:
• The dominant allele A causes normal pigmentation
• The recessive allele a causes albinism
• AA and aa are homozygous, while Aa is heterozygous
• Mating two heterozygous parents for albinism gives these probability of genotypes
• 25% AA (normal pigmentation)
• 50% Aa (normal pigmentation)
• 25% aa (albinism)

Incomplete Dominance

• Heterozygous individuals have an intermediate phenotype
• They may have symptoms, but less intense than homozygous individuals
• Sickling gene example:
• SS = normal hemoglobin (Hb) is made
• Ss = sickle-cell trait where both mutated and normal Hb are made
• These people can suffer a sickle-cell crisis with prolonged reduction in O2
• ss = sickle-cell anemia, makes only mutated Hb
• These people are more susceptible to sickle-cell crisis even with short O2 reduction

Multiple Allele Inheritance

• Genes exhibiting more than two allele forms
• Example: ABO blood groups have three alleles: IA, IB, and I
• The combination of two out of the three alleles determines a person's ABO blood type
• IA and IB are codominant and expressed if present, which results in type AB
• The allele, i, is recessive type O
• Heterozygotes express the dominant A or B so:
• OA is type A blood
• OB is type B blood
• Homozygote with ii results in OO, so type O blood

Sex-Linked Inheritance

• Sex-linked inheritance refers to inherited traits determined by genes on sex chromosomes
• Genes found only on the X chromosome are X-linked genes
• X-linked recessive alleles are always expressed in males because there is no Y counterpart to mask them
• Females must have recessive alleles on both X chromosomes to express an X-linked condition
• X-linked recessive conditions are passed from mothers to sons
• Examples: hemophilia or red-green color blindness

Polygene Inheritance

• Traits that result from actions of several gene pairs at different locations
• The more genes involved in a trait, the more phenotypic variation is seen
• Results in continuous (quantitative) phenotypic variation between two extremes
• Examples: skin color and height
• Polygenic inheritance for skin color:
• Alleles for dark skin (ABC) are incompletely dominant over those for light skin (abc)
• First-generation offspring of AABBCC x aabbcc cross results in all heterozygotes with intermediate pigmentation
• Second-generation offspring have even wider variation, which would lead to a bell-shaped curve

Environmental Factors’ Effect on Gene Expression

• The environment can override or influence gene expression
• Maternal factors (drugs, pathogens) can alter normal gene expression in embryonic development
• Thalidomide causes embryos to develop phenotypes not directed by their genes because of the drug
• Environmental factors influence gene expression after birth
• Poor nutrition can affect brain growth, body development, and height
• Childhood hormonal deficits lead to abnormal skeletal growth and proportions

Regulation of Gene Expression

• Three levels of controls are found in the human genome
• First layer: protein-coding genes
• Involve less than 2% of a cell’s DNA
• DNA serves as the "blueprint" for protein synthesis
• Second layer: small noncoding RNAs (sncRNA)
• Found in non-protein-coding DNA, or 80% of genome
• Examples: microRNAs (miRNAs) and small interfering RNAs (siRNAs) that reduce the expression of particular genes
• They may be used to treat diseases by interfering with the expression of certain genes
• Third layer: epigenetic marks
• Stored in proteins and chemical groups that bind to DNA and package chromatin
• Chemical tags (methyl and acetyl groups) determine if DNA is available for transcription (acetylation) or silenced (methylation)
• Genomic imprinting refers to certain genes tagged with methyl groups during gametogenesis to identify them as maternal or paternal
• This is essential for normal development
• Allows embryo to express only the mother's or father's gene

Extranuclear (Mitochondrial) Inheritance

• Not all DNA is located in the cell's nucleus
• Mitochondria contain 37 of their genes, referred to as mitochondrial DNA (mtDNA)
• Mitochondria are transmitted to the embryo by the mother in the cytoplasm of the egg
• Errors in mtDNA are linked to rare disorders
• Usually, these are problems associated with oxidative phosphorylation (cellular respiration)
• Can cause muscle and neurological problems, possibly Alzheimer's and Parkinson's diseases

Genetic Screening

• Genetic screening and genetic counseling provide information and options for prospective parents
• Newborn infants are routinely screened for genetic disorders
• Examples: congenital hip dysplasia, imperforate anus, PKU, and other metabolic disorders
• Other examples: screening adult children of parents with Huntington's disease and testing fetus of 35-year-old woman for trisomy-21 (Down syndrome)

Carrier Recognition

• Two major ways to identify carrier of detrimental genes are:
• Pedigrees: Traces a genetic trait through several generations to help predict future risks
• Genetic counselors collect information on family members and construct the pedigree (family tree)
• Blood tests: Simple blood tests screen for the sickling gene in heterozygotes
• Sophisticated blood chemistry tests and DNA probes can detect other unexpressed recessive genes
• Tay-Sachs and cystic fibrosis genes can be identified with such tests

Human Gene Therapy

• Gene therapy may alleviate or cure disorders
• Genetic engineering has potential to replace defective genes:
• Defective cells can be infected with a genetically engineered virus containing a functional gene
• A "corrected" gene can be injected directly into cells
• However, it is prohibitively expensive, and raises many ethical, religious, and societal questions