Genetics Quiz: Mendel and DNA Structure

Nutritional Biochemistry

• The subject matter is inheritance, DNA mutations, and DNA repair.
• The course code is DIET413/BHCS1019.
• The lecturer is Dr Nathaniel Clark FHEA RNutr MRSB.
• The lecturer's email address is [email protected].

DNA Structure and Function

• The smallest unit of DNA is a nucleotide composed of a nitrogenous base, pentose sugar, and a phosphate group.
• Polynucleotide chains are formed through phosphodiester bonds linking phosphate group and sugar between nucleotides.
• DNA wraps around histone proteins to condense into chromatin.
• DNA undergoes transcription and translation to produce functional proteins (phenotype).
• These processes are controlled by enzymes.
• DNA is also present in mitochondria and is involved in respiration (lacks introns).
• Genetic mutations in DNA can cause various disease states.

Learning Outcomes

• Outline genetic inheritance (autosomal and sex inheritance).
• Describe different types of mutations.
• Determine how DNA damage can be repaired.
• Provide a brief overview of various types of cancer.

Genotype and Phenotype

• Genotype is the unique DNA sequence of an organism.
• Phenotype is the effect of a mutation on an organism.
• Changes to the genotype can influence the phenotype.
• Inheritable phenotypes are based on genotype.

Mendelian Inheritance

• Gregor Mendel's work forms the basis of modern genetics.
• Traits are controlled by factors (genes) that exist in pairs (one from each parent).
• Factors can be dominant (heterozygous) or recessive (homozygous).

Mendelian Inheritance - Experiments

• The first experiment crossed homozygous tall plants with homozygous short plants, resulting in all tall offspring.
• The second experiment crossed heterozygous tall plants, resulting in a 3:1 ratio of tall to short offspring.
• This demonstrated the concept of dominant and recessive characteristics.

Mendelian Inheritance - Punnett's Square

• Punnett squares are used to visualize patterns of inheritance.
• Alleles for traits are represented, and potential combinations are shown, demonstrating possible outcomes.

Mendelian Inheritance - Limitations

• Dominance may not apply in all cases of contrasting characteristics.
• Blending inheritance may occur in some cases.
• Multiple genes can interact (epistasis) resulting in complex inheritance patterns.
• Genetic predisposition increases the risk of certain diseases but does not cause them directly..

Patterns of Inheritance

• Mendelian inheritance describes traits controlled by a single gene.
• Autosomal inheritance involves genes on non-sex chromosomes.
• Sex-linked inheritance involves genes on sex chromosomes (X and Y).
• Examples of inheritance patterns include autosomal dominant, autosomal recessive, sex-linked dominant, and sex-linked recessive.

Autosomal Dominant Inheritance

• Traits/disorders are carried on the dominant gene.
• Transmission is easily visualized using a Punnett square.
• Examples include familial hypercholesterolemia, polycystic kidney disease, and Huntington's disease.

Autosomal Recessive Inheritance

• Transmission depends on whether one or both parents carry the recessive allele.
• Traits/disorders are more likely to skip generations if passed from a recessive allele.
• Examples include haemochromatosis and cystic fibrosis.

Activity

• Determine the likelihood of an affected individual passing on a disease to their children.
• Examples include haemochromatosis, normal heterozygous partner and dominant homozygous partner.

Sex-Linked Disorders

• Disorders are carried on X or Y chromosomes.
• X-linked disorders are more common as the X chromosome is larger.
• X-linked recessive disorders can be passed from a carrier mother to affected male/carrier female offspring through a Punnett Square.
• Examples include Fragile X syndrome and Haemophilia.

X-linked Recessive Disorders - Transmission

• Transmission depends on whether the mother or father is carrying the relevant allele.
• The concepts of "affected male" and "carrier female" are important

X-linked Recessive Disorders - Common Disorders

• Examples include Fragile X syndrome, haemophilia, and Duchenne muscular dystrophy.

X-linked Dominant Disorders

• Very rare; different risk in offspring depending on if the affected parent is male or female.

Mutations

• DNA sequence preservation is crucial for protein function.
• The base sequence determines the protein structure.
• One human genome contains approximately 3 billion base pairs, distributed across 23 chromosomes.
• DNA mutations may involve one or more bases.

Mutants vs. Wild Types

• Wild type describes the usual phenotype of an organism.
• Mutant describes an organism with a changed phenotype due to a mutation.
• Point mutations affect single bases within the DNA (gene) sequence, whereas gross mutations affect larger stretches of the DNA (chromosome) sequence.

Point Mutations

• Understanding triplet coding is essential for understanding point mutation consequences.
• Main types:
  • Silent mutations: altered nucleotide but same amino acid produced.
  • Frameshift mutations: insertions or deletions that cause a shift in the reading frame, changing multiple amino acids.
  • Missense mutations: altered nucleotide causing a different amino acid to be produced (minor protein changes).
  • Nonsense mutations: an altered nucleotide that produces a premature stop codon (causes a severely truncated and likely non-functional protein).

Point Mutations - Silent Mutations

• Silent mutations occur when nucleotide change does not result in a different amino acid being produced.
• DNA sequence and amino acid remain the same, but redundancy within the genetic code remains.
• These occur as polymorphisms, showing variability within different individuals.

Point Mutations - Frameshift Mutations

• Frameshift mutations occur when a base pair is added or removed from the DNA sequence, causing a shift in the reading frame during transcription.
• This leads to a change in the amino acid sequence that can cause serious effects, and often produces a truncated protein and a mutant phenotype.

Point Mutations - Missense Mutations

• A missense mutation involves a base substitution that results in a different amino acid being produced.
• This can cause minor to moderate changes to the protein depending on the amino acid substitution.

Point Mutations - Nonsense Mutations

• A nonsense mutation involves a base substitution that produces a premature stop codon.
• This leads to a prematurely truncated protein that is likely non-functional.

Gross Mutations (large-scale)

• These are substantial alterations in DNA, often involving long DNA stretches.
• Common types of large-scale mutations include deletions, insertions, translocations, inversions, and duplications.

Gross Mutations - Deletions

• Loss of part of a chromosome or a gene which can result in a total or incomplete protein loss.
• Loss of gene function or changes to the regulatory regions can cause serious abnormalities.
• Can result in diseases like Duchenne muscular dystrophy.

Gross Mutations - Insertions

• Insertion of extra base pairs, possibly from another chromosome.
• Significant shift in reading frame, producing mutant outcomes.
• Often causes a large frameshift mutation, producing a truncated or non-functional protein.

Gross Mutations - Translocations

• Exchange of DNA sections between chromosomes.
• This can create hybrid proteins, leading to diseases like chronic myelogenous leukemia (and/or Down syndrome).

Gross Mutations - Inversions

• Inversions involve the rotation of a DNA segment within a chromosome.
• Orientation change of the nucleotides will cause issues processing/building the functional protein.
• It can result in disorders like some haemophilias.

Gross Mutations - Duplications

• Duplication involves a segment of DNA being copied and inserted next to the original segment.
• This results in an extra copy of a segment/gene, which can result in new genetic material and, under the right circumstances, possibly leading to development of useful characteristics in an organism/species.

DNA Damage and Repair

• DNA is constantly under attack (from various sources).
• Organisms have complex DNA repair mechanisms, including base excision repair, nucleotide excision repair, and mismatch repair.

Cancer

• Cell growth and differentiation are tightly controlled.
• Unsuccessful DNA repair mechanisms, in conjunction with environmental factors/habits, can lead to genetic mutations which disrupt cell growth and/or cause the uncontrollable growth seen in cancer.
• Lifestyle factors and exposure to environmental carcinogens can negatively impact cell regulation, leading to potentially uncontrolled growth and potentially tumours.
• Damage to genes controlling cell growth or damage to tumour suppressor genes can contribute to cancer development.

Proto-oncogenes

• Proto-oncogenes are involved in regulating cell growth/division and are crucial to maintaining a healthy organism.
• Mutation/over activation of a proto-oncogene becomes an oncogene and negatively impacts normal cell function.
• Abnormal/disrupted oncogene/normal cell function/growth can lead to the development of cancer.
• Oncogenes cause cancer onset and accelerate cells/tumours.

p53

• Major regulator controlling cell division and death.
• Responds to cellular stresses (including DNA damage) and regulates apoptosis, including DNA repair.
• Damage to p53 can lead to uncontrolled cellular growth, thereby contributing to cancer.

Telomeres

• Protect chromosome ends from degradation or end-to-end fusion.
• Telomeres shorten during cell division.
• Telomerase maintains telomere length.
• Immortality of cancer cells is linked to telomerase expression; thus, enabling cancer cells to continue dividing without telomere shortening affecting them.

Variation in Cancer Risk (among individuals and tissues)

• Cancer risk in different tissues correlates with the total number of cell divisions.
• Environmental factors contribute to cancer risk, but random mutations during cell division play a significant role.

Breast Cancer (linked to BRCA genes)

• BRCA1 and BRCA2 are DNA repair genes that can cause inherited predisposition to breast cancer.
• Prophylactic mastectomy can significantly reduce breast cancer risk, especially for those with inherited mutations in the BRCA genes.

Colorectal Cancer

• Colorectal cancer risk is influenced by predisposition genotypes and environmental factors.
• Lynch Syndrome increases the risk of various cancers including colorectal cancer.
• Familial adenomatous polyposis is a less common cause of colorectal cancer.

Familial Adenomatous Polyposis

• Autosomal dominant disorder characterized by the development of multiple polyps in the colon.
• Polyps are adenomas with potential to become cancerous.
• Untreated cases frequently lead to colorectal cancer by the age of 40.
• May be associated with increased risk of other upper gastrointestinal cancers.

Summary

• Mendelian inheritance demonstrates autosomal and sex-linked traits' inheritance and expression.
• DNA can be altered through point or gross mutations.
• Repair mechanisms (e.g., base excision, nucleotide excision, mismatch repair), when compromised, may lead to diseases like cancer.

Test your knowledge on key concepts in genetics, including DNA structure, Mendelian inheritance, and mutation types. From the basics of DNA units to the specifics of genotypes and phenotypes, this quiz covers essential topics that form the foundation of genetic science.