Basic Genetics

Structural Relationship between Chromosomes, DNA, and Genes

Genetics Foundation: Genetics is defined as the study of heredity and variations in organisms. Characteristics are passed from parents to offspring through genes.
Chromosomes: These are thread-like structures made up of DNA (Deoxyribonucleic acid) and proteins (histones).
Gene: A segment of the DNA molecule of a chromosome. It serves as the basic unit of heredity.
Locus (Gene Locus): The specific, fixed position of a gene on a chromosome.
Genetic Information and Protein Synthesis: The DNA of a gene carries genetic information for making a polypeptide that can form various types of proteins, which include:
- Structural proteins: Used for building cells and tissues.
- Enzymes: Used for catalysing metabolic reactions.
- Hormones: Used for maintaining homeostasis (internal balance).
- Carrier proteins or channel proteins: Used for regulating the transport of molecules across the cell membrane.
Gene Function: By controlling the types of proteins a cell makes, genes determine the body characteristics or traits (特徵) of an organism. Each inherited characteristic is controlled by a single gene or several genes.
Alleles: A gene can exist in two or more alternative forms called alleles. These are situated on the same locus of a pair of homologous chromosomes.

Deoxyribonucleic Acids (DNA) and Nucleic Acids

Classification: DNA belongs to a group of large molecules called nucleic acids. This group also includes RNA (Ribonucleic acid).
Chemical Structure of Nucleic Acids: A nucleic acid is a long chain of nucleotides. Each nucleotide consists of three components:
1. A $5$ -carbon sugar (deoxyribose in DNA, ribose in RNA).
2. A phosphate group.
3. A nitrogenous base.
Formation of Polynucleotides: Nucleotides are joined to one another between the sugar of one nucleotide and the phosphate group of the next. This resulting structure is a polynucleotide.

Comparison of DNA and RNA

Sugar Type:
- DNA: Deoxyribose sugar.
- RNA: Ribose sugar.
Nitrogenous Bases:
- DNA: Adenine (A), Thymine (T), Cytosine (C), and Guanine (G).
- RNA: Adenine (A), Uracil (U), Cytosine (C), and Guanine (G).
Chain Structure:
- DNA: Composed of two polynucleotide chains (double-stranded).
- RNA: Composed of one polynucleotide chain (single-stranded).

The Watson-Crick Model of DNA

Physical Structure: A DNA molecule consists of two polynucleotide chains. These chains run in opposite directions (antiparallel) and twist to form a double helix.
Base Pairing Rules: These are known as complementary base pairing rules. Adenine (A) pairs only with Thymine (T) by hydrogen bonds, and Cytosine (C) pairs only with Guanine (G).
Relationship of Structure to Function:
- The base sequence of a gene determines the amino acid sequence in a polypeptide.
- Base sequences form the genetic code (遺傳密碼).
- DNA can carry a large amount of genetic information.
- DNA is a stable molecule.
- DNA can replicate accurately.

DNA Replication Process

Bond Breaking: The two DNA strands are held together by weak hydrogen bonds between the bases. These bonds break, and the two DNA strands separate.
Template Mechanism: Each individual DNA strand acts as a template for the synthesis of a new DNA strand.
Enzymatic Activity: An enzyme called DNA polymerase catalyses the addition of free nucleotides that are complementary to each template strand.
Result: Two identical DNA molecules are formed. Each new molecule is semi-conservative, containing one original strand and one newly synthesized strand.

Monohybrid Inheritance and Mendel’s Laws

Definition: Monohybrid inheritance (單基因遺傳) is the inheritance of a single characteristic controlled by a single gene.
Mendel’s Pea Plant Experiment:
- Method: Gregor Mendel cross-pollinated pea plants with contrasting characters (e.g., tall vs. short stems).
- Steps:
  1. Remove stamens from one flower to prevent self-pollination.
  2. Dust pollen grains from the second variety onto the stigma of the first.
  3. Enclose the flower in a paper bag and wait for fertilization.
  4. Collect and sow the resulting seeds.
- Results: All plants in the first filial generation ( $F_1$ ) were tall. When Mendel allowed the $F_1$ tall plants to self-pollinate, the second filial generation ( $F_2$ ) showed a ratio of approximately $3$ tall plants to $1$ short plant.
Mendel’s First Law (Law of Segregation): During gamete formation, each allele in a pair separates (segregates) so that each gamete receives only one allele from each pair.

Genetics Glossary and Definitions

Dominant Allele: An allele that determines the character the organism displays even in a heterozygous condition. Represented by a capital letter (e.g., $T$ ).
Recessive Allele: An allele that can only express itself in a homozygous condition. Represented by a small letter (e.g., $t$ ).
Phenotype: The observable character or physical appearance of an individual (e.g., Tall).
Genotype: The genetic make-up of an individual (e.g., $TT$ , $Tt$ , or $tt$ ).
Homozygous: An organism whose genotype contains two identical alleles for a characteristic (e.g., $TT$ or $tt$ ). If they have identical recessive alleles, they are a homozygous recessive or double recessive.
Heterozygous: An organism whose genotype contains two different alleles for a characteristic (e.g., $Tt$ ).
Hybrid: An individual resulting from crossing two pure-bred (homozygous) parents of the same species that are genetically different for the studied characteristic.

Common Human Monohybrid Characteristics

Widow’s peak (Dominant) vs. Straight hairline (Recessive).
Free earlobe (Dominant) vs. Attached earlobe (Recessive).
Dimple (Dominant) vs. No dimple (Recessive).
Straight thumb (Dominant) vs. Hitchhiker’s thumb (Recessive).
Curved little finger (Dominant) vs. Straight little finger (Recessive).

Probability and Outcome in Genetics

The outcome of any specific cross is independent of and not related to any other.
Genetic diagrams and Punnett squares provide expected or theoretical results.
To achieve actual results close to expected results, a large sample size is required.

Monohybrid Test Crosses

Purpose: To determine the unknown genotype of an organism displaying a dominant character.
Procedure: Cross the organism of unknown genotype with a homozygous recessive organism.
Interpretations:
- If all offspring show the dominant character, the unknown organism is homozygous dominant.
- If offspring show dominant and recessive characters in a $1:1$ ratio, the unknown organism is heterozygous.

Pedigree Analysis in Humans

Deducing Dominance Steps:
1. Locate parents with the same phenotype who have an offspring with a different phenotype.
2. The offspring must have inherited a recessive allele from each parent.
3. Since the parents do not display that phenotype but carry the allele, they must be heterozygous.
4. In a heterozygous state, only the dominant allele is expressed; thus the parental phenotype is dominant and the offspring phenotype is recessive.

Dihybrid Inheritance

Definition: The inheritance of two pairs of contrasting characters simultaneously, involving two genes located on different (non-homologous) chromosomes.
Mendel’s Dihybrid Experiment: Mendel crossed plants with round, yellow seeds with plants with wrinkled, green seeds.
- $F_1$ Result: All seeds were round and yellow.
- $F_2$ Result (after self-pollination): A phenotypic ratio of $9$ (Round, Yellow) : $3$ (Round, Green) : $3$ (Wrinkled, Yellow) : $1$ (Wrinkled, Green).
Mendel’s Second Law (Law of Independent Assortment): The separation of alleles for one gene is independent of the separation of alleles for other genes during gamete formation.
Dihybrid Test Cross Conditions:
- $1$ Phenotype (all dominant): Unknown is homozygous dominant for both ( $RRYY$ ).
- $2$ Phenotypes ( $1:1$ ratio): Unknown is homozygous for one and heterozygous for the other (e.g., $RRYy$ ).
- $4$ Phenotypes ( $1:1:1:1$ ratio): Unknown is heterozygous for both ( $RrYy$ ).

Human Blood Groups (ABO System)

Blood Types: A, B, AB, and O.
Antigen/Antibody Specifics:
- Group A: Antigen A on RBC; Antibody B in plasma.
- Group B: Antigen B on RBC; Antibody A in plasma.
- Group AB: Both Antigen A and B on RBC; No antibody in plasma.
- Group O: No antigens on RBC; Both Antibody A and B in plasma.
Multiple Alleles: The single gene for blood group has three alleles:
1. $I^A$ : Responsible for antigen A.
2. $I^B$ : Responsible for antigen B.
3. $i$ (or $I^O$ ): Produces no antigen.
Co-dominance: Alleles $I^A$ and $I^B$ are co-dominant, meaning both are expressed in the phenotype when present together ( $I^AI^B$ ). Both are dominant over allele $i$ .

Sex Determination and Sex Linkage

Chromosomes: Humans have $23$ pairs of chromosomes. $22$ pairs are autosomes, and the $23$ rd pair is the sex chromosomes.
Determination: Females are $XX$ . Males are $XY$ . Males produce $50\%$ X-bearing and $50\%$ Y-bearing sperm, whereas females produce only X-bearing ova.
Sex Linkage: Genes located on sex chromosomes are sex-linked genes. Most are located on the X chromosome (X-linked).
Red-green Color Blindness: An X-linked recessive disorder.
- Let $X^B$ represent the allele for normal vision and $X^b$ for color blindness.
- Genotypes:
  - $X^BX^B$ : Normal female.
  - $X^BX^b$ : Female carrier (normal phenotype).
  - $X^bX^b$ : Color-blind female.
  - $X^BY$ : Normal male.
  - $X^bY$ : Color-blind male.
- Males are more frequently affected because they have only one X chromosome; a single recessive allele on that chromosome will express the disorder.

Variations in Populations

Continuous Variation: A variation showing a continuous range of phenotypes between two extremes (e.g., human height, weight). Graphically represented by a normal distribution curve. Usually controlled by many genes (polygenic) and influenced by the environment.
Discontinuous Variation: A variation with a few distinct phenotypes and no intermediate forms (e.g., tongue rolling, ABO blood groups). Controlled by one or a few genes and usually unaffected by environmental factors.

Causes of Genetic Variation

Independent Assortment: Random alignment and separation of homologous chromosomes during meiosis.
Crossing Over: Exchange of genetic segments between homologous chromosomes during meiosis.
Random Fertilization: Any sperm can fuse with any egg, creating unique allele combinations in the zygote.
Mutations: Sudden and permanent changes in DNA structure or chromosome number. Only mutations in gametes (germ-line cells) are heritable.
Environmental Factors: Light (chlorophyll production) and temperature (e.g., wing development in fruit flies) can affect how a genotype develops into a phenotype.

Case Studies and Practical Discussion

Corn Kernels (HKDSE 2012): Sweet corn kernels contain soluble sugars and become wrinkled when they dry because they lose more water via osmosis than starchy corn kernels.
Identical Twins Research: Using identical twins allows researchers to control for genetic factors (since they share $100\%$ of DNA), making it easier to identify environmental influences on traits like tongue rolling.
Blood Donation Rules: Men can donate blood up to $5$ times a year (interval $≥ 75$ days), while women can donate up to $4$ times (interval $≥ 105$ days), often due to physiological differences like iron loss during menstruation.
Pure-bred Pets vs. Hybrids: Pure-bred pets have a higher risk of genetic diseases because they are bred from close relatives with similar gene pools. This increases the probability of offspring being homozygous recessive for deleterious alleles. In contrast, hybrid pets from diverse gene pools are more likely to be heterozygous, where dominant alleles can mask harmful recessive ones.