QC

Pedigree Analysis and Inheritance Patterns

American Kennel Club Pedigree (Page 1)

This page displays a certified pedigree from the American Kennel Club (AKC), established in 1884, for a German Shepherd Dog female named VAN CLEVES CASSANDRA V KALEEF.

Key Information:

  • Name: VAN CLEVES CASSANDRA V KALEEF

  • Breed: German Shepherd Dog

  • Sex: Female

  • Color: Black & Tan (BLK & TN)

  • Date Whelped: June 4, 2000

  • Breeder: SHEREE W MOSES/JAMES A MOSES

  • Certification Date: Compiled from official Stud Book records on October 11, 2005.

Lineage Details:

Sire's Line:

  • Sire: CH WELOVE DU CHIEN'S 'R' MAN (DL50826105, 07-95)

    • OFA25G, OFEL25, BLK & TN, AKC DNA #V22411

    • Sire's Sire: CH KISMET'S SIGHT FOR SORE EYES PT (DL64767204, 11-97)

      • OFA25G, OFEL25, BLK & TN, AKC DNA #V71190

    • Sire's Dam: KISMET'S SWEETHEART DEAL (DA017403, 10-93)

      • OFA27G, OFEL27, BLK & TN

  • Dam (of Sire): CH TINDROCK-KALEEF ABOUT THYME HSAS (DL78487001, 08-00)

    • OFA26G, OFEL26, BLK & TN, AKC DNA #V166975

    • Dam's Sire (of Sire): KEN-DELAINE'S KATARINA (DL49658104, 06-96)

      • OFA29G, OFEL29, BLK & TN

    • Dam's Dam (of Sire): CH KEN-DELAINE'S MASTERCHARGE (D38305504, 06-92)

      • OFA37F, OFEL37, BLK & TIN

Dam's Line:

  • Dam: CH KALEEF'S BLONDIE HS (DL67255801, 02-99)

    • BLK & TN

    • Dam's Sire: VAN CLEVES CASSANDRA V KALEEF (DL83383208)

      • OFA45G, OFEL45, AKC DNA #V346794

    • Dam's Dam: BRAMBLEWOOD'S DIEDRE V NOCHEE II (D558000, 05-91)

      • OFA29G, BLK & TN

  • Dam (of Dam): CH COVY-TUCKER HILL'S STORM BRIER CD (D963662, 06-92)

    • OFA32G, OFEL32, BLK & TN, AKC DNA #V50951

    • Dam's Sire (of Dam): CH BRIER HILL'S STORM BUDDY (DL50215102, 04-97)

      • OFA36G, OFEL36, BLK & TN

    • Dam's Dam (of Dam): KARIZMA'S TIMBER OF BRIER HILL (D696465, 06-92)

      • OFA27G, OFEL27, BLK & TN

  • Dam's Dam's Dam: CH HOLLOW HILLS' SIERRA V CHERPA (DL38846101, 04-97)

    • OFA24G, OFEL24, BLK & RD

    • Dam's Dam's Dam's Sire: CH LOTHARIO OF HEINERBURG CD (WF218383, 01-84)

      • OFA57G, BLK & RD

    • Dam's Dam's Dam's Dam: CHERPA'S HOLLOW HILLS' STEJAN (D894765, 01-92)

      • OFA29G, OFEL29, BLK & TN

OFA and OFEL Codes: These refer to certifications from the Orthopedic Foundation for Animals, indicating evaluations for diseases like hip and elbow dysplasia, with codes (e.g., G for good, F for fair) and age at evaluation.

Chapter 6: Pedigree Analysis (Page 2)

This chapter outlines the key topics to be covered in pedigree analysis:

  • Why pedigrees? (6.1)

  • Parts of a pedigree (6.2)

  • Autosomes vs. sex chromosomes (4.1)

  • Inheritance patterns (6.2, 11.4)

  • Pedigrees and probability (6)

Challenges in Human Genetics (Page 3)

Human genetics research faces several distinct difficulties when compared to studying other organisms:

  • Small number of offspring: Humans typically have a small number of children, leading to a lack of statistical significance in observing inheritance patterns. For example, if a couple has 5 daughters, calculating the probability of this specific outcome can be done, but it doesn't give a robust statistical sample for broader genetic inferences compared to organisms with hundreds of offspring.

  • Experimental crosses not feasible/unethical: Unlike plants or laboratory animals, performing controlled experimental crosses in humans is unethical and impossible.

  • Long generation time: Humans have a long generation time, meaning many years pass between parent and offspring generations. This makes observing inheritance patterns across multiple generations a very slow process.

Reliance on Pre-existing Family Trees: Due to these challenges, human geneticists rely heavily on pre-existing family trees, also known as pedigrees, to trace the mode of inheritance for various traits and diseases.

Pedigree Structure and Example (Page 4)

Pedigrees are standardized charts used to represent family relationships and inheritance of specific traits. Key symbols and notations used in pedigrees:

  • Squares: Represent males.

  • Circles: Represent females.

  • Shaded shapes: Indicate individuals affected by the trait in question.

  • Unshaded shapes: Indicate unaffected individuals.

  • Horizontal lines between a male and female: Represent a mating/reproduction.

  • Vertical lines descending from a mating line: Connect to the offspring.

  • Horizontal lines connecting offspring: Show siblings.

  • Roman numerals (e.g., I, II, III, IV): Denote generations.

  • Arabic numerals (e.g., 1, 2, 3): Identify individuals within each generation.

  • Diamond shapes: Can represent individuals of unknown sex.

  • Double horizontal line: Indicates a consanguineous mating (mating between close relatives).

  • Half-shaded shapes (not shown in example but sometimes used): Can represent carriers for recessive traits.

  • Genotypes: Can be inferred or directly labeled (e.g., A/A, A/a, a/a for dominant/recessive alleles).

Example Pedigree Interpretation (4 Generations Shown):

  • Generation I: Two individuals, a male and a female.

  • Generation II: Shows offspring from Generation I, with some detailed genotypes (A/A, A/a) and a consanguineous mating.

  • Generation III: Further offspring, including an affected individual and inferred genotypes (A/a for a carrier).

  • Generation IV: Shows offspring from Generation III, including two affected individuals (a/a).

Assessing Affected Individuals in the Pedigree (Page 5)

Based on the example pedigree provided on Page 4, which shows shaded individuals as affected:

  • Number of affected individuals: 4 individuals are affected.

    • One in Generation II.

    • One in Generation III.

    • Two in Generation IV.

Autosomes vs. Sex Chromosomes (Page 6)

Chromosomes are categorized into two main types:

  • Autosomes:

    • These are chromosomes that do not determine sex.

    • Both males and females typically have two copies of each autosome (one from each parent).

  • Sex Chromosomes:

    • These are chromosomes that determine the sex of an individual.

    • In mammals, males have one X chromosome and one Y chromosome (XY).

    • In mammals, females have two X chromosomes (XX).

Number of Autosomes in Humans (Page 7)

Considering the human karyotype:

  • Humans typically have 22 pairs of autosomes.

  • The total number of chromosome pairs is 23: 22 autosomal pairs and 1 pair of sex chromosomes.

Sex Determination in Mammals (Page 8)

Sex in mammals is determined by the sex chromosomes following a Mendelian pattern:

  • P generation (Parents):

    • Male: XY

    • Female: XX

  • Meiosis (Gamete Formation):

    • Male gametes (sperm): X and Y

    • Female gametes (eggs): X and X

  • Fertilization (F1 generation):

    • If an X sperm fertilizes an X egg, the offspring is XX (Female).

    • If a Y sperm fertilizes an X egg, the offspring is XY (Male).

  • Conclusion: This mechanism results in a 1:1 sex ratio for offspring.

Paternity of Y Chromosome (Page 9)

Question: Males only give their Y chromosome to their daughters.

Answer: False.

  • Males (XY) give their Y chromosome to all of their sons and none of their daughters.

  • Daughters receive an X chromosome from their father.

Maternal X Chromosome Contribution (Page 10)

Question: Females can give an X chromosome to children of either sex.

Answer: True.

  • Females (XX) have only X chromosomes to contribute to their offspring.

  • Therefore, an egg will always carry an X chromosome.

  • This X chromosome can be passed to either a son (XY) or a daughter (XX).

Four Basic Inheritance Patterns (Page 11)

When analyzing pedigrees to determine the mode of inheritance, two fundamental questions are addressed:

  1. How many copies of the allele are needed to see the phenotype? (This determines dominance or recessiveness).

  2. Is the gene located on a sex chromosome, or an autosome? (This determines if it's sex-linked or autosomal).

Combining these questions leads to four basic inheritance patterns:

  • Autosomal recessive

  • Autosomal dominant

  • Sex-linked recessive (typically X-linked recessive in humans)

  • Sex-linked dominant (typically X-linked dominant in humans)

Autosomal Recessive Inheritance (Page 12)

Key observable patterns for autosomal recessive traits:

  • Unaffected parents can have affected offspring: This is a hallmark sign, as two heterozygous carriers (unaffected) can produce a homozygous recessive (affected) child.

  • Both male and female offspring are affected at similar frequencies: The gene is on an autosome, so sex does not influence the expression frequency.

Autosomal Recessive Pedigree Example (Page 13)

Referring to the example pedigree (similar to Page 4, with shaded shapes indicating affected individuals, which are homozygous recessive a/a):

  • Generation I: Unaffected parents (e.g., one A/a and one A/A or A/a).

  • Generation II: An affected individual (a/a) appears. This strongly suggests that the parents in Generation I were both carriers (A/a).

  • Generation III: Shows unaffected individuals, some of whom are carriers. Another affected individual (a/a) appears, again implying their parents were at least carriers.

  • Generation IV: Two affected individuals (a/a) are shown.

This pattern confirms that unaffected parents can produce affected offspring, which is characteristic of recessive inheritance.

Genotypes for Autosomal Recessive Disease (Page 14)

Question: What must be the genotypes of two unaffected parents that have an offspring affected by an autosomal recessive disease?

Answer: 4. heterozygous

  • If the disease is autosomal recessive, an affected offspring must have the genotype a/a.

  • For two unaffected parents to produce an a/a offspring, both parents must carry the recessive allele (a) but not express the disease themselves. This means both parents must be heterozygous (A/a).

Probability of Mutant Allele Transmission (Page 15)

Question: What is the probability that a heterozygous individual will pass the mutant allele on to an offspring?

Answer: 3. 1/2

  • A heterozygous individual has two different alleles for a gene, for example, A/a.

  • According to Mendel's Law of Segregation, each gamete (sperm or egg) receives only one of the two alleles with equal probability.

  • Therefore, the probability of passing on the mutant allele (a) is 1/2.

Autosomal Dominant Inheritance (Page 16)

Key observable patterns for autosomal dominant traits:

  • Affected individuals have at least one affected parent: Since only one copy of the dominant allele is needed for the phenotype, offspring cannot be affected unless at least one parent carries the dominant allele and is therefore affected.

  • Affected parent of either sex can pass on to offspring of either sex: The gene is on an autosome, so transmission is not sex-specific to the offspring.

  • Typically, the trait appears in every generation (no