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Pedigrees & Abnormal Genetics - Vocabulary Flashcards

Pedigrees & Inheritance

  • Pedigree: a chart that shows the presence or absence of a trait within a family across generations.
  • Purpose: analyze inheritance patterns, determine genotypes, identify phenotypes, and predict how traits may be passed on.
  • Pedigrees use standardized symbols to represent family members and relationships.

Key Genetic Concepts

  • Genotype: genetic makeup of an organism (e.g., TT).
  • Phenotype: physical characteristics (e.g., tall).
  • Dominant allele: allele phenotypically expressed over another allele.
  • Recessive allele: allele expressed only in the absence of a dominant allele.
  • Autosomal dominant: trait located on an autosome (non-sex chromosome).
  • Sex-linked trait: trait located on one of the sex chromosomes (often X-linked).
  • Homozygous: two identical alleles for a gene (e.g., TT, tt).
  • Heterozygous: two different alleles for a gene (e.g., Tt).
  • Note: There is a transcript error where “Heterozvaous” appears; correct term is heterozygous.

Pedigree Symbols (Common Symbols)

  • Female: circle; Male: square.
  • Affected with trait: shaded symbol.
  • Marriage line: horizontal line connecting spouses.
  • Deceased: small cross or slash through symbol (often a diagonal line).
  • Twins: twin lines or brackets.
  • Adopted: dashed or dotted line to indicate non-biological relation.
  • Miscarriage: line with a small symbol or marker.
  • Line of descent: vertical line tracing ancestry.
  • Sibling line: horizontal line connecting siblings.
  • Generation number: Roman numeral or number beside each generation to label generations.

Reading a Pedigree: Dominant vs Recessive; Autosomal vs Sex-Linked

  • Determine if the trait is dominant or recessive:
    • If dominant, at least one parent must show the trait. Dominant traits do not skip generations.
    • If recessive, neither parent must be affected (parents can be heterozygous).
  • Determine autosomal vs sex-linked (often X-linked):
    • X-linked traits often affect males more; females can be carriers.
    • Autosomal traits affect males and females roughly equally.

Example: Autosomal Dominant Trait – Freckles

  • Example allele notation: freckles (F) is dominant to no freckles (f).
  • Pedigree scenario: a grandmother (I generation) with freckles (Ff or FF) has three children; two of them show freckles (II-3 and II-5).
  • Likely inheritance: autosomal dominant; affected individuals appear in multiple generations.
  • Inheritance note: If one parent is affected and the other is not, children have a 50% chance to be affected (assuming heterozygous affected parent, i.e., Ff × ff gives 50% Ff).
  • Genotype examples:
    • If parent genotypes are FF × ff, all offspring are affected (100%).
    • If parent genotypes are Ff × ff, half offspring are affected: P( ext{affected}) = frac{1}{2}.

Example: Sickle Cell Anemia Pedigree (Autosomal Recessive)

  • Sickle cell disease is autosomal recessive (need two recessive alleles, hh).
  • Key notation used in pedigrees:
    • H = Healthy
    • h = Sickle cell disease
  • Typical interpretation: Affected individuals have the recessive genotype hh; carriers have Hh and are usually healthy.
  • Pedigree analysis involves identifying carrier parents who may produce affected offspring (e.g., two carriers producing an affected child).

Tongue Rolling and Other Dominant/Recessive Traits (Pedigree Examples)

  • Tongue rolling example shows a dominant trait (roller) vs recessive (non-roller).
  • Common notation:
    • Roller = dominant allele; Non-roller = recessive allele.
    • Genotypes: Roller could be TT or Tt; Non-roller is tt.
  • Example cross: a tongue roller (TT) female × non-roller (tt) male:
    • All offspring are rollers: genotype Tt for all progeny.
    • Phenotype: Roller in all offspring (dominant trait expressed).
  • Pedigree interpretation: If one parent is TT and the other is tt, offspring are 100% Tt; if cross is Aa × Aa, phenotypes depend on dominance relationships.

Pedigree: Hemophilia (X-Linked) Example

  • Hemophilia is an X-linked trait (often X-linked recessive).
  • Key notation: XA = normal X chromosome; Xa = X chromosome with the allele for disease.
  • Typical inheritance pattern:
    • Males have only one X chromosome; if they inherit Xa, they express the disease.
    • Females can be carriers (XaX) or affected (XaXa) if they inherit Xa from both parents.
  • In royal family pedigree example, genotypes are matched to identify who is XA or Xa across generations; males are often affected while females are carriers or unaffected depending on genotype.

Common Mistakes in Pedigrees (Note: This section appears garbled in the transcript but indicates common pitfalls when interpreting pedigrees)

  • Mislabeling autosomal vs sex-linked traits.
  • Assuming traits skip generations without evidence.
  • Incorrectly inferring carrier status from affected individuals.
  • Misinterpreting shaded vs unshaded symbols without considering heterozygotes.
  • Not accounting for consanguinity or adoption in the lineage where relevant.

Basic Genetics & Genetic Testing – Ethical, Legal, and Social Context

  • Basic idea: Genetic testing can reveal inherited risks or current genetic conditions.
  • Map of the human genome: conceptual map of all genes and their locations.
  • Privacy and ownership: who owns genetic information?
  • Morality and law: privacy concerns, potential for DNA patenting, and access control (employers, military, insurers, courts).
  • The line between medical treatment and enhancement in the future.
  • Ethical questions raised by prenatal testing and potential decisions (e.g., abortion vs life with disability).
  • Insurance, legal, and social implications of genetic data.

Map of the Genome, Privacy, and Legal Considerations

  • Privacy concerns about genetic data in medical records.
  • Potential for DNA sequences to be patented or used by third parties.
  • Who should have access to genetic information (patients, doctors, insurers, employers, government, researchers)?
  • Implications for discrimination and consent in genetic testing.

Mutations: Definition and Classification

  • Mutations are changes in the nucleotide sequence of DNA.
  • Major classification:
    • Hereditary (germline) mutations: inherited from a parent; present in egg or sperm; passed to offspring; present in virtually every cell.
    • Acquired (somatic) mutations: occur during life; present only in certain cells and cannot be passed to offspring.
  • Somatic mutations can be caused by environmental factors (e.g., UV radiation) or replication errors during cell division.
  • Germline mutations are what underlie inherited diseases.

What Are Mutations? (Continued)

  • Mutations may occur in somatic cells (not passed to offspring) or gametes (eggs and sperm) and be passed to offspring if in germ cells.
  • They lead to changes in the nucleotide sequence of DNA.

Genetic Diseases, Testing, and Prevalence

  • Over 4000 human diseases are thought to be inherited.
  • Tests exist for 50+ conditions (examples: breast cancer risk, fragile X syndrome, Huntington disease, cystic fibrosis, muscular dystrophy like Duchenne).
  • Tests are approximately 99% accurate in many contexts.
  • Embryo testing via in-vitro fertilization (IVF) prior to implantation can test embryos for certain genetic conditions.

Ethical Issues in Genetic Information

  • If prenatal testing reveals bad news, options include abortion or continuing with a child who has disease.
  • Should genetics be part of medical records?
  • Who owns genetic information?
  • Can DNA sequences be patented?
  • Who should have access to genetic data (employers, military, insurance companies, courts)?
  • Where is the line between medical treatment and enhancement in the future?

Gene Therapy Using an Adenovirus Vector (Basic Mechanism)

  • Concept: Use a virus (adenovirus) as a vector to deliver modified DNA into human cells.
  • Steps:
    • Virus enters cell through the cell membrane.
    • Gene therapy DNA is packaged into the virus; new gene is incorporated into the viral genome.
    • Virus disassembles and delivers DNA into the nucleus via the nuclear pore.
    • mRNA is transcribed from the introduced gene, providing a blueprint for protein production.
    • RNA Polymerase transcribes the genetic information from the new gene into mRNA, which is used to synthesize the therapeutic protein.
  • Key components mentioned: penton proteins, capsid, nucleus, nuclear pore, mRNA, RNA polymerase, and viral DNA packaging.
  • Goal: Correct or modify genetic function within patient cells to treat disease.

Notational Quick Reference (Selected Points)

  • Dominant vs Recessive:
    • Dominant trait expressed when at least one dominant allele is present.
    • Recessive trait expressed only when both alleles are recessive.
  • Autosome vs X-linkage:
    • Autosomal: trait on non-sex chromosome; affects sexes roughly equally.
    • X-linked: trait on X chromosome; males more often affected for recessive X-linked traits.
  • Common genotype notations:
    • Dominant homozygous: AA
    • Heterozygous: Aa
    • Recessive homozygous: aa
  • Basic Punnett outcomes (illustrative formulas):
    • Autosomal dominant cross (Aa × Aa): P( ext{affected}) = P(AA) + P(Aa) = frac{1}{4} + frac{1}{2} = frac{3}{4}
    • Autosomal recessive cross (Aa × Aa): P( ext{affected}) = P(aa) = frac{1}{4}
    • X-linked recessive cross (carrier mother X^A X^a, father X^A Y):
    • Sons affected: P( ext{son affected}) = frac{1}{2}
    • Daughters carriers: P( ext{daughter carrier}) = frac{1}{2}
  • Example trait lists (dominant vs recessive):
    • Dominant: eye color (brown if dominant), tongue-rolling ability, right-handedness, free earlobes, thick lips, Rh positive, normal color vision, almond-shaped eyes (in context), etc.
    • Recessive: blue eyes, non-rolling tongue, left-handedness (in some datasets), attached earlobes, thin lips, Rh negative, color blindness, rounder face features, etc.

Connections to Prior Concepts and Real-World Relevance

  • Pedigree analysis connects to Mendelian genetics and Punnett squares for predicting inheritance patterns.
  • Understanding autosomal vs sex-linked inheritance informs genetic counseling and testing strategies.
  • Knowledge of mutations underpins disease risk assessment and preventive medicine.
  • Genetic testing and privacy considerations impact healthcare policy and ethics.
  • Gene therapy represents translational applications from basic genetics to potential treatments.

Practical Implications and Takeaways

  • Pedigrees are powerful for spotting inheritance patterns but require careful symbol interpretation and awareness of generation-to-generation skipping possibilities due to trait type.
  • Dominant traits do not skip generations (unless new de novo mutations or incomplete penetrance are involved).
  • Recessive traits may skip generations; carrier mothers can propagate recessive diseases when mating with a carrier or affected partner.
  • X-linked diseases commonly present in males while females may be carriers; family history helps identify risk for siblings and offspring.
  • Genetic testing raises ethical questions about privacy, ownership, and access that society must address as technology advances.
  • Gene therapy using viral vectors illustrates a real-world approach to treating genetic disorders but also requires careful consideration of safety, ethics, and long-term effects.