Genetics and Inheritance Notes

Genetics and inheritance: comprehensive notes

• Genetics is the study of genes, heredity, and genetic variation in living organisms.

  • Genes are segments of DNA that encode instructions for protein production.
  • Humans have 23 pairs of chromosomes, 46 total, with DNA inherited from both biological parents.

• Basic genetic terms

  • Gene: a unit of heredity passed from parent to offspring.
  • Allele: a variant form of a gene; can be dominant or recessive.
  • Genotype: the genetic makeup of an individual.
  • Phenotype: an observable trait.
  • Mutation: a permanent change in the DNA sequence that may or may not cause disease.

• Patterns of inheritance

  • Autosomal dominant: only one mutated gene is needed to express the trait.
  • Autosomal recessive: two copies of the mutated gene are required to express the trait.
  • X-linked: mutation occurs on the X chromosome.
  • X-linked recessive or X-linked dominant: depending on the mutation, different patterns of transmission.
  • Mitochondrial (maternal) inheritance: passed from mother to offspring via mitochondrial DNA.
  • Multifactorial disorders and nontraditional inheritance patterns also exist.

• Examples (brief)

  • Autosomal dominant examples: Huntington's disease, Marfan syndrome, familial hypercholesterolemia, neurofibromatosis type 1.
  • Autosomal recessive examples: cystic fibrosis, sickle cell anemia, Tay-Sachs disease, phenylketonuria (PKU).
  • X-linked recessive examples: hemophilia A and B, Duchenne muscular dystrophy, color blindness.
  • X-linked dominant examples: Rett syndrome, Fragile X syndrome.

• What is a karyotype?

  • A karyotype is a picture/diagram showing the number and structure of a person’s chromosomes.
  • Used to examine chromosome number, size, shape, and banding pattern.
  • Humans normally have 46 chromosomes arranged in 23 pairs: 22 autosomes and 1 pair of sex chromosomes.
  • Sex chromosomes: XX for females, XY for males.

• How is a karyotype made?

  • Cells are collected (commonly white blood cells) from blood, amniotic fluid, or bone marrow.
  • Cells are cultured and then stopped during metaphase of mitosis when chromosomes are most visible.
  • Chromosomes are stained, photographed, and arranged by size and centromere position.

• What can a karyotype detect?

  • Numerical abnormalities (abnormal chromosome number):
  • Trisomy (three copies of a chromosome) e.g., Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), Patau syndrome (Trisomy 13).
  • Monosomy (one copy of a chromosome) e.g., Turner syndrome (Monosomy X).
  • Structural abnormalities: deletion, duplication, translocation, inversion.
  • Sex chromosome disorders: Klinefelter syndrome (XXY), Turner syndrome (monosomy X), XXX, Jacobs syndrome (XYY).

• Clinical uses of karyotyping

  • Prenatal diagnosis: amniocentesis or chorionic villus sampling (CVS).
  • Infertility or recurrent miscarriage evaluation.
  • Diagnosis of genetic syndromes.
  • Cancer genetics (e.g., leukemia with Philadelphia chromosome).
  • Evaluation of ambiguous genitalia or abnormal pubertal development.

• Chromosomal abnormalities: categories and examples

  • Numerical abnormalities (due to nondisjunction):
  • Trisomies: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards), Trisomy 13 (Patau).
    • Down syndrome features: intellectual disability, flat facial profile, single transverse palmar crease, hypotonia, congenital heart defects; increased risk of leukemia and Alzheimer’s disease.
    • Edwards syndrome features: severe developmental delay, clenched fists, rocker-bottom feet, heart defects; poor prognosis; often die in infancy.
    • Patau syndrome features: cleft lip/palate, polydactyly, microcephaly, severe CNS and heart defects; often fatal in early infancy.
  • Monosomy: Turner syndrome (45,X): features include short stature, webbed neck, infertility, absence of secondary sexual characteristics; often identified at puberty due to amenorrhea.
  • Sex chromosome abnormalities: Klinefelter syndrome (XXY), XXX syndrome (Triple X), Jacob’s syndrome (XYY).
  • Structural abnormalities: deletions, duplications, translocations, inversions (segment rearrangements).

• Genetic evaluation and counseling

  • Genetic counseling is a process to help individuals and families understand how genetic conditions might affect them and their children.
  • Ideal time for counseling is before conception.
  • Who should receive genetic counseling (examples from transcript):
  • Individuals with personal or family histories of genetic conditions (birth defects, developmental delays, chromosomal abnormalities, hereditary cancer syndromes, single-gene disorders like CF or SCA).
  • Personal or family history of cancer (early-onset cancers, multiple related cancers, hereditary cancer syndromes, Ashkenazi Jewish ancestry).
  • Couples planning pregnancy or advanced maternal age (>35 years).
  • Abnormal prenatal screening or ultrasound findings.
  • Carrier screening showing risk for recessive disorders.
  • Recurrent pregnancy losses or stillbirths.
  • Consanguinity (first/second cousins).
  • Newborns or children with unexplained developmental delays, autism spectrum disorders, dysmorphic features, seizures, or neurologic concerns.
  • Ethnic backgrounds at higher risk for specific gene disorders (e.g., Ashkenazi Jews, African/ African American, Southeast Asian, or Mediterranean descent).
  • Fertility issues or use of assisted reproductive technologies (ART), unknown infertility, multiple miscarriages, donor eggs/sperm usage, or prerimplantation genetic diagnosis candidates.
  • Known hereditary disease in the family or known carriers of autosomal recessive or X-linked conditions.
  • LGBTQ individuals or couples using assisted reproduction.

• Roles of genetic counselors

  • Interpret family and medical histories.
  • Assess risk of disease recurrence.
  • Explain genetic testing options, results, and limitations.
  • Provide psychosocial support and assist with decision making.
  • Guide medical management or reproductive choices.

• Nursing and provider implications

  • Support patients through testing, diagnosis, and counseling.
  • Prepare patients for procedures such as amniocentesis.
  • Educate about inheritance patterns, outcomes, and prognosis.
  • Collaborate with genetic counselors and specialists.
  • Provide psychosocial support for families.
  • Monitor developmental milestones and coordinate care for affected children.

• Other responsibilities

  • Identify at-risk patients.
  • Provide basic education on genetics and inheritance.
  • Refer patients appropriately for genetic counseling and support informed decision making.

• Practical and ethical implications

  • Non-directive counseling respects patient autonomy in testing and reproductive decisions.
  • Privacy and potential discrimination concerns with genetic information.
  • Impacts on family planning, pregnancy management, and long-term care planning.

• Key numerical probabilities and formulas (illustrative Punnett outcomes)

  • Autosomal recessive cross (Aa x Aa):
  • Genotype distribution: P(AA)= frac{1}{4}, \, P(Aa)= frac{1}{2}, \, P(aa)= frac{1}{4}
  • Phenotype: 25% affected, 50% carriers, 25% unaffected (assuming complete penetrance and expressivity).
  • Autosomal dominant cross (Aa x aa) or (AA x Aa):
  • Offspring affected probability: P(affected)= frac{1}{2}
  • X-linked recessive (mother carrier X^A X^a; father normal X^A Y):
  • Sons affected: P(son ext{ affected})= frac{1}{2}
  • Daughters carriers: P(daughter ext{ carrier})= frac{1}{2}
  • X-linked dominant (mutant allele X^D):
  • Affected fathers pass the trait to all daughters but no sons (sons inherit Y from father).
  • Affected mothers pass to 50% of children (both sons and daughters) in the typical paternal/ maternal cross.

• Connections to foundational principles and real-world relevance

  • Mendelian inheritance underpins autosomal dominant/recessive and X-linked patterns.
  • Central dogma (DNA -> RNA -> protein) explains how gene variants alter phenotypes.
  • Chromosome-level abnormalities influence development and cancer risk; prenatal testing can inform pregnancy management.
  • Ethical considerations influence how and when testing is offered, and how results are communicated and acted upon.

• Quick reference for common conditions mentioned

  • Down syndrome: Trisomy 21; features include intellectual disability, flat facial profile, single palmar crease, hypotonia, congenital heart defects.
  • Edwards syndrome: Trisomy 18; severe developmental delay, clenched fists, rocker-bottom feet, heart defects.
  • Patau syndrome: Trisomy 13; cleft lip/palate, polydactyly, microcephaly, severe CNS/heart defects.
  • Turner syndrome: Monosomy X; short stature, webbed neck, infertility, lack of secondary sexual characteristics.
  • Klinefelter syndrome: XXY; typical male phenotype with some features like hypogonadism.
  • Triple X syndrome: XXX; often tall stature, sometimes developmental concerns.
  • Jacob’s syndrome: XYY; tall stature, sometimes learning difficulties.
  • Huntington’s disease: autosomal dominant; adult-onset neurodegenerative disorder.
  • Marfan syndrome: autosomal dominant; connective tissue disorder affecting eyes, aorta, skeleton.
  • Cystic fibrosis: autosomal recessive; thick mucus production affecting lungs and digestive system.
  • Sickle cell anemia: autosomal recessive; abnormal hemoglobin causing hemolysis and pain crises.
  • Tay-Sachs disease: autosomal recessive; progressive neurodegeneration.
  • PKU: autosomal recessive; amino acid metabolism disorder.
  • Hemophilias (A and B), Duchenne muscular dystrophy, color blindness: X-linked recessive.
  • Rett syndrome, Fragile X syndrome: X-linked dominant.

• Notes on terminology and cautions

  • Transcript includes some typos (e.g., Trisomy 21, Down syndrome; Trisomy 13 often called Patau; Turner vs Turner’s; “XX for females, XY for males” is correct; ensure exact naming in formal settings).
  • Always integrate genetic information with clinical findings, family history, and patient values.

• Summary

  • Genetics explains how traits are inherited, how chromosomal abnormalities arise, and how this knowledge informs prenatal testing, diagnosis, counseling, and management.
  • Understanding probabilities helps in assessing recurrence risks and making informed decisions.
  • Genetic counseling and coordinated care are essential for patients and families navigating risk, testing options, and outcomes.