Classical Genetics

Gregor Mendel

The 19th-century scientist who studied pea plants and first discovered the mathematical patterns of hereditary trait inheritance; developed the three laws of inheritance that form the foundation of classical genetics

Dominance

The relationship between alleles in which one allele (dominant) masks the expression of the other (recessive) when both are present in a heterozygous organism

Mendel's Law of Dominance

Some alleles are dominant and others are recessive; an organism with at least one dominant allele for a gene will exhibit the dominant phenotype; the recessive phenotype is only expressed when no dominant allele is present

Dominant allele

An allele that is expressed in the phenotype whenever it is present, even if only one copy exists; represented by an uppercase letter

Recessive allele

An allele whose phenotype is only expressed when no dominant allele is present (i.e., in a homozygous recessive individual); represented by a lowercase letter

Mendel's Law of Segregation

During gamete formation, the two alleles for each gene separate so that each gamete carries only one allele for each gene; results from the separation of homologous chromosomes during meiosis I

Segregation

The separation of allele pairs during meiosis I, ensuring each resulting gamete carries only one allele per gene

Mendel's Law of Independent Assortment

Genes for different traits on different (non-homologous) chromosomes can segregate independently during gamete formation, producing new combinations of alleles; results from random chromosome alignment at metaphase I

Independent assortment

The random orientation of homologous chromosome pairs at metaphase I, which means alleles for genes on different chromosomes are distributed to gametes in all possible combinations

Nondisjunction

The failure of chromosomes or chromatids to separate properly during meiosis; produces gametes with an extra or missing chromosome, leading to conditions like trisomy or monosomy in offspring

Trisomy

A chromosomal condition in which a cell has three copies of a particular chromosome instead of two; results from fertilization involving a gamete that received an extra chromosome due to nondisjunction

Monosomy

A chromosomal condition in which a cell has only one copy of a particular chromosome; results from fertilization involving a gamete that is missing a chromosome due to nondisjunction

Polyploidy

A condition in which cells contain more than two complete sets of chromosomes; occurs when nondisjunction affects all chromosomes simultaneously; the gametes and resulting zygote have an entire extra set of chromosomes

Genotype

The specific combination of alleles an organism possesses for a given gene or set of genes

Phenotype

The observable physical expression of an organism's genotype; the outward appearance or measurable trait produced by the genotype in the context of the environment

Homozygous

A genotype in which both alleles for a gene are identical (e.g., BB or bb); can be homozygous dominant or homozygous recessive

Heterozygous

A genotype in which the two alleles for a gene are different (e.g., Bb); the dominant allele is expressed in the phenotype

Ploidy

The number of complete sets of chromosomes in a cell; diploid cells have two sets, haploid cells have one set

Punnett square

A grid-based tool used to predict the possible genotype and phenotype ratios of offspring from a genetic cross; columns represent one parent's gametes and rows represent the other's; named for Cambridge biologist Reginald Punnett (1875–1967)

Parental generation (P)

The first two organisms crossed in a genetics experiment; also called P1 and P2; the starting point of a series of crosses

First filial generation (F1)

The offspring of the parental (P) generation cross; the first generation of offspring

Second filial generation (F2)

The offspring produced by crossing two F1 individuals; often shows a classic 3:1 phenotypic ratio in a monohybrid cross

Monohybrid cross

A genetic cross that examines the inheritance of a single gene with two alleles; produces a 3:1 phenotype ratio and a 1:2:1 genotype ratio in the F2 generation when both parents are heterozygous

Dihybrid cross

A genetic cross that examines the simultaneous inheritance of two genes on different chromosomes; produces a 9:3:3:1 phenotypic ratio in the F2 generation when both parents are heterozygous for both traits

FOIL method

A technique for determining all possible gamete combinations in a dihybrid cross; stands for First, Outer, Inner, Last — the four combinations of alleles from a doubly heterozygous parent (e.g., PpSs produces PS, Ps, pS, ps)

Number of gamete types formula

2^n, where n is the number of heterozygous allele pairs in a parent; used to calculate how many different gamete types a parent can produce (e.g., a parent heterozygous for 2 genes produces 2² = 4 gamete types)

9:3:3:1 ratio

The expected phenotypic ratio in the F2 generation of a dihybrid cross between two parents heterozygous for both traits on separate chromosomes; 9 dominant/dominant : 3 dominant/recessive : 3 recessive/dominant : 1 recessive/recessive

3:1 ratio

The expected phenotypic ratio in the F2 generation of a monohybrid cross between two heterozygous parents; 3 offspring show the dominant phenotype for every 1 that shows the recessive phenotype

1:2:1 ratio

The expected genotypic ratio in the F2 of a monohybrid cross (1 homozygous dominant : 2 heterozygous : 1 homozygous recessive); also the phenotypic ratio seen in incomplete dominance and codominance crosses

Linked genes

Genes located on the same chromosome that tend to be inherited together; the closer together two genes are on a chromosome, the less likely they are to be separated by crossing-over

Recombination (genetic)

The exchange of DNA segments between homologous chromosomes during crossing-over in meiosis I; can separate linked genes, producing new allele combinations in offspring; greater physical distance between genes means greater chance of separation

Sex chromosomes

The X and Y chromosomes; the 23rd pair of human chromosomes; responsible for sex determination and certain sex-linked traits; females are XX, males are XY

Autosomes

The 22 pairs of human chromosomes (numbered 1–22) that are not sex chromosomes; involved in general inheritance rather than sex determination

Sex-linked trait

A trait controlled by a gene located on a sex chromosome (usually the X chromosome); inheritance patterns differ between males and females because males have only one X chromosome

X-linked inheritance

A pattern of inheritance in which the gene controlling a trait is located on the X chromosome; recessive X-linked alleles are always expressed in males (who have only one X) but may be masked in females (who have two X chromosomes)

Hemizygous

Describes a male who has only one copy of an X-linked gene (since he has only one X chromosome); a recessive X-linked allele is always expressed in a hemizygous male

X-linked recessive trait

A trait caused by a recessive allele on the X chromosome; expressed in all males who carry the allele (hemizygous) but only in females who are homozygous recessive; examples include color blindness and white eyes in Drosophila

Carrier (genetics)

An individual who carries one copy of a recessive allele (usually on the X chromosome) without showing the associated phenotype; can pass the allele to offspring; often refers to heterozygous females in X-linked conditions

Sex-linked allele notation

Alleles on sex chromosomes are written as superscripts on the X or Y symbol (e.g., X^R for dominant red eyes, X^r for recessive white eyes in Drosophila); dominant alleles use uppercase letters, recessive alleles use lowercase

X-inactivation

The random inactivation of one X chromosome in each somatic cell of a female; on average half a female's cells use one X and half use the other; if skewed, a carrier female may show symptoms of an X-linked condition

Thomas Hunt Morgan

Early 20th-century geneticist who used Drosophila to provide the first evidence for the chromosome theory of inheritance; discovered X-linked inheritance by studying white-eye mutations in fruit flies

Chromosome theory of inheritance

The theory that chromosomes carry genes and that all genes on a single chromosome tend to be inherited together (linked); first supported by Morgan's work with Drosophila

Drosophila melanogaster

The common fruit fly; a model organism widely used in genetics research; has a short generation time (~12 days), only 4 pairs of chromosomes, is inexpensive to maintain, and shows extensive genomic homology with humans

Complete dominance

A pattern of inheritance in which the heterozygous phenotype is identical to the homozygous dominant phenotype; only one allele is expressed; produces a 3:1 phenotypic ratio in F2

Incomplete dominance

A pattern of inheritance in which the heterozygous phenotype is intermediate between the two homozygous phenotypes; neither allele completely masks the other; produces a 1:2:1 phenotypic ratio in F2 (e.g., red × white snapdragons → pink F1)

Codominance

A pattern of inheritance in which both alleles are fully expressed simultaneously in the heterozygous phenotype; produces a 1:2:1 phenotypic ratio in F2 (e.g., red and white camellia cross → petals with both red and white patches in F1)

Multiple alleles

A situation in which more than two alleles exist for a single gene in a population, even though each individual can carry at most two; example: the ABO blood type system has three alleles (A, B, and O)

ABO blood type system

A human blood typing system controlled by three alleles of one gene: I^A (codes for A surface antigen), I^B (codes for B surface antigen), and i (recessive, produces no antigen); A and B are codominant; O is recessive

Blood type A

A blood type phenotype in which red blood cells carry the A surface antigen; possible genotypes are I^A I^A (homozygous) or I^A i (heterozygous)

Blood type B

A blood type phenotype in which red blood cells carry the B surface antigen; possible genotypes are I^B I^B (homozygous) or I^B i (heterozygous)

Blood type AB

A blood type phenotype in which red blood cells carry both A and B surface antigens; genotype is I^A I^B; results from codominance of the A and B alleles

Blood type O

A blood type phenotype in which red blood cells carry neither A nor B surface antigens; genotype is ii (homozygous recessive); the only blood type that requires two recessive alleles

Rh factor

A blood antigen system based on the presence (Rh+) or absence (Rh−) of specific Rh surface antigens on red blood cells; Rh+ is dominant over Rh−; Rh− individuals can produce Rh+ antibodies upon exposure to Rh+ blood

Rh incompatibility

A medical concern in which a Rh− mother may produce antibodies against Rh+ antigens after exposure to fetal blood (e.g., during childbirth); in subsequent pregnancies, maternal antibodies can cross the placenta and attack a Rh+ fetus

Pedigree

A diagram that shows family history and genetic relationships in a standardized format; uses circles for females, squares for males, filled symbols for affected individuals; used to identify patterns of inheritance and at-risk family members

Proband

The individual in a pedigree who serves as the starting point for a genetic study of a family; typically the first affected person identified

Consultand

The patient or individual who seeks genetic information or counseling in a clinical genetics setting

Autosomal dominant inheritance

A pattern of inheritance in which one mutated copy of a gene on an autosome is sufficient to cause the condition; affected individuals in every generation; both males and females can be affected equally (e.g., HNPCC/Lynch syndrome)

Autosomal recessive inheritance

A pattern of inheritance in which two mutated copies of an autosomal gene are required to cause the condition; carriers (one copy) are unaffected; can skip generations

Genetic testing

Any medical test that identifies changes in chromosomes, genes, or proteins; often identifies specific changes that may predispose an individual to a particular condition; requires a DNA sample sent to a certified laboratory

HNPCC (Lynch syndrome)

Hereditary nonpolyposis colorectal cancer; an autosomal dominant cancer syndrome caused by inherited mutations in caretaker/DNA repair genes (MLH1, MSH2, MSH6, PMS2); accounts for ~3–5% of colorectal cancers; individuals with one inherited mutation have an ~80% lifetime risk of developing colorectal cancer

Caretaker genes

Genes that scan the genome to identify and repair DNA mutations; mutations in both copies lead to accumulation of additional DNA damage; the four HNPCC caretaker genes are MLH1, MSH2, MSH6, and PMS2

Hereditary vs. acquired cancer

Hereditary cancers (~5%) are caused primarily by an inherited mutation present in every cell; acquired (somatic) cancers result from DNA damage accumulated during a person's lifetime and are far more common

Charcot-Marie-Tooth disease (X-linked)

An inherited neuropathy (peripheral nerve disease) caused by a pathogenic variant in the GJB1 gene on the X chromosome; X-linked inheritance; males are typically more severely affected; carrier females may show variable symptoms due to X-inactivation skewing

GJB1 gene

The gene on the X chromosome whose pathogenic variants cause Charcot-Marie-Tooth disease, X-linked type 1; a single hemizygous variant in a male causes the condition

Pathogenic variant

A genetic change (mutation) that is classified as disease-causing based on evidence from genetic studies; also called a disease-causing variant