Sexual Reproduction and Inheritance

Development and its Significance

• Development is crucial for understanding:
  • Normal biological processes.
  • Abnormalities.
  • Positioning of adult structures.

Simultaneous Processes in Development

• Multiple processes occur simultaneously:
  • Gastrulation.
  • Neurulation.
  • Organogenesis.
• Tissues form concurrently, sometimes using the same genes.

Heart Hand Syndrome (Holt-Oram Syndrome)

• Example of developmental biology importance:
  • Thumb looks like a finger.
  • Enlarged heart (atrial defect).
• Indicates:
  • Thumb and heart form at the same time.
  • Involves the same gene (TBX5).
• TBX5:
  • Involved in thumb formation.
  • Involved in heart development.
  • Its function varies based on the environment.
• Clinical relevance: Abnormal thumb shape may indicate heart issues.

Impact of Developmental Biology on Society

• In vitro fertilization (IVF):
  • Result of developmental biology research.
  • Used by a significant number of couples (mentioned 25%, but confirm).
• Understanding foods to avoid during pregnancy to prevent birth defects.
• Screening for genetic mutations.
• Future possibilities:
  • Tissue regeneration.
  • Better disease models.
  • Organ harvesting and transplantation.
  • Embryonic stem cells.
  • Cloning (ethical considerations).

Fertilization

• Activates the egg to begin development.
• Restores the diploid number of chromosomes (46 in humans, 23 pairs).
• Sperm nucleus migrates to the female pronucleus to form a zygote.
• Timing varies: 12 minutes in sea urchins, hours in humans.
• Initiates signaling and molecular distribution among blastomeres.

Cleavage

• Zygote undergoes divisions (cleavages).
• No overall growth of the embryo until gastrulation.

Types of Sexual Reproduction

• Diplomatic (vertebrates, including humans):
  • Two haploid gametes fuse to form a diploid individual.
• Other organisms (plants, fungi) can have diploid gametes and haploid individuals.
• Vertebrate method considered successful for dominance.

Sex Determination in Humans

• Determined at conception.
• SRY region:
  • Specific region on the Y chromosome.
  • Without SRY, cannot be male.
• Default vertebrate state: female.

SRY Gene and Sex Determination

• Females typically have Wnt4, which activates DAX1 and other genes, leading to ovary development.
• SRY gene inhibits Wnt4 expression.
• SRY gene allows activation of SOX9, leading to testes development.
• Mutations can lead to:
  • XX individuals with the SRY region (rare).
  • XY individuals missing the SRY gene, resulting in a non-male phenotype.

Sex Determination in Other Species

• Birds (Z and W chromosomes):
  • Default state: male.
  • Femaleness requires overriding maleness.
• Mice and fish: Similar to humans, default state is female.
• Commonality: Region on one chromosome that triggers male development.

Environmental Influences on Sex Determination

• Turtles, crocodiles, and alligators: Temperature-dependent sex determination.
• Thermosensitive period: Influences sex determination.
• Example: Turtles: Cold temperatures favor male development, warm temperatures favor female development.
• Mechanism: Temperature affects SOX9 expression.

Why Sexual Reproduction?

• Disadvantages:
  • Need to find a partner.
  • Decreased reproductive capacity with age.
• Benefits: The most significant is Variability
  • Genetic crossover during meiosis leads to unique individuals.
  • The number of combinations of genotypes and crossover events is very large, approximately 2^{23,000}
  • This crossover ensures no two people (except identical twins) look the same.

Meiosis and Genetic Variation

• Male germ cell: Sperm.
• Female germ cell: Secondary oocyte.
• Meiosis: Reduces chromosome number to haploid (23).
• Fertilization: Restores diploid number (46).
• Sex is determined at conception.
• Meiosis separates homologous chromosomes and allows genetic crossover.

Stages of Meiosis

• Prophase: Chromosomes materialize and align.
• Metaphase: Chromosomes line up for cell division.
• Cell division: Chromosomes split into pairs, reducing chromosome number.
• Separation of chromatids: Results in four cells, each with one set of chromosomes (haploid).

Crossover Event in Meiosis I

• Occurs in the first metaphase.
• Parts of chromosomes exchange (e.g., blue to red).
• Happens every time, in all chromosomes.
• Results in haploid cells with different chromosome combinations.
• Contributes to massive variation when combined with gametes from another partner.
• Ensures siblings share traits but are not identical.

Differences in Meiosis Between Males and Females

• Males: Meiosis occurs continuously during sperm production.
• Females: Meiosis I occurs in early development, meiosis II only completes upon fertilization.
• Eggs remain arrested between meiosis I and II for a long time.

Crossing Over and Recombination

• Crossing over: Exchange of genetic information, leading to recombinant chromatids.
• Increases genetic variation of gametes.
• Consequences:
  • Offspring are never identical.
  • Variability within the population.
  • Potential for malformations if crossing over is uneven.

Inheritance of Characteristics

• Crossing over allows changes in heritability.
• Genetic maps can be created based on recombination frequency.
• Recombination frequency:
  • Tends to be higher at the ends of chromosomes.
  • Can be used to map genes based on observed characteristics.

Genetic Maps and Recombination Frequency

• High recombination frequency: Genes are further apart on the chromosome.
• Low recombination frequency: Genes are close together (linked).
• Linked genes: Lower chance of recombination, reduces mutation risk.

Alfred Sturtevant

• Proposed using recombination frequency to map genes on chromosomes.
• Genes are located close together on the chromosome are considered linked and have a lower frequency.
• Chromosomes are made of thousands and thousands of genes.

Sex-Linked Inheritance

• Two types:
  • Recessive: Requires the genetic variation on both X chromosomes (females) or a single X chromosome (males) to manifest the condition.
  • Dominant: A mutation on a single X chromosome is enough to cause the condition.
• Examples of X-linked conditions: Hemophilia and muscular dystrophy.

Inheritance Patterns

• Father with X-linked recessive condition:
  • Daughters will be carriers.
  • Sons will be unaffected (Y chromosome is normal).
• Mother with X-linked recessive condition:
  • 50% chance of passing it to sons.
  • 50% chance of passing carrier status to daughters.

X-Linked Inheritance Examples

• Males are hemizygous for genes on the X chromosome because they can get it from their mom or their dad.
• Dominant female with hemizygous recessive male: All offspring will be dominant because they'll have the X chromosome from from mom, which has got the mutation.
• Homozygous recessive female with homozygous dominant male: Daughters have the dominant phenotype, and males are carriers.

Color Blindness as an X-Linked Recessive Trait

• Mom is a carrier:
  • One son will be colorblind.
  • One son will be unaffected.
  • Daughters will be carriers.

Aneuploidy and Chromosome Abnormalities

• Aneuploidy: Abnormal number of chromosomes.
• Can result from incorrect recombination during meiosis.
• Duplication of a chromosome (e.g., trisomy 13, Down syndrome).
• Missing parts of chromosomes.
• Leads to birth defects.

Extra Sex Chromosomes and Chromosome Duplications

• Extra sex chromosomes (X and Y): Lead to disorders of sexual development.
• Famous chromosome duplications: Down syndrome, Edwards syndrome, and Patau syndrome.
• Caused by failure of chromosomes to properly split and conjoin.

Chromosome Anomalies and Pregnancy

• Chromosome anomalies typically occur early in development.
• Most result in early pregnancy loss (spontaneous abortion).
• Conditions like Down syndrome and Turner syndrome are compatible with life, but most are not.
• Significance: Fifty percent of all conceptions end in spontaneous abortion, and fifty percent of these are due to chromosome abnormalities, i.e., twenty five percent of all conceptuses have a chromosomal anomaly.
• Chromosome abnormalities account for seven percent of major live birth differences.

Summary

• Sex determination.
• Meiosis (creating haploid gametes).
• Exchange of genetic information.
• Chromosome numbers and abnormalities.