How Genes Are Transmitted from Generation to Generation Chapter 4

Central Points  Genes are transmitted from generation to generation  Traits are inherited according to predictable rules

Gregor Mendel – The Father of Genetics

4.1 How Are Genes Transmitted?  Experiments with pea plants in 1800s  Traits, distinguishing characteristics  Specific patterns in the way traits were passed from parent to offspring

Different Plant Heights

Mendel’s Experiments  Some traits disappeared in the first generation of offspring (all tall)  Reappeared in 3:1 ratio (tall:short)  Dominant trait present in the first-generation offspring (tall)  Recessive trait absent in first generation but reappeared in the next generation (short)

Traits Are Passed by Genes  “Factors” or genes transmitted from parent to offspring  Each parent carries a pair of genes for a trait but contributes only one gene to each offspring  Separation of gene pair occurs during meiosis

Genes  Alleles: variations of a gene  Geneticists use letters for each allele.  Homozygous: identical alleles of a gene TT or tt  Heterozygous: nonidentical alleles Tt

Phenotype and Genotype  Phenotype: what an organism looks like tall or short  Genotype: genetic makeup TT, Tt, and tt  Identical phenotypes may have different genotypes TT or Tt have tall phenotype

Mendel’s Law of Segregation  Two copies of each gene separate during meiosis  One copy of each gene in the sperm or egg  Each parent gives one copy of each gene

Sorting of Alleles

Mendel’s Law of Independent Assortment  Members of a gene pair segregate into gametes independently of other gene pairs  Gametes can have different combinations of parental genes

Human Traits: Albinism  Pigmentation dominant and lack of pigment recessive AA, Aa: Pigmented aa: Albino  Both parents Aa, each child has 25% chance of being albino (3:1 ratio)

Fig. 4-3a, p. 61 Aa × A a A a Two carriers of albinism have a child. The male and female can contribute either an A allele or an a allele to the gamete.

Fig. 4-3b, p. 61 Genotype Phenotype Aa 1 AA 2 Aa 3/4 normal coloring A AA normal Aa normal 1 aa 1/4 albino a Aa normal aa albino This shows the possible genotypes and phenotypes of the o ff spring. The possible o ff spring and allele combinations are shown above.

Pedigree 1  Shows all family members and identifies those affected with the genetic disorder

Pedigree 2

Pedigree Symbols

p. 62 Male Female Mating Mating between relatives (consanguinous) I Parents and children. Roman numerals symbolize generations. Arabic numbers symbolize birth order within generation (boy, girl, boy) II 123 I, II, III, etc. = each generation 1, 2, 3, etc. = individuals within a generation

p. 62 or Una ff ected individual or A ff ected individual orKnown heterozygotes orProband; a person in family who is the focus of the pedigree PP I, II, III, etc. = each generation 1, 2, 3, etc. = individuals within a generation

Pedigree Symbols

Proband  Person who is the focus of the pedigree  Indicated by an arrow and the letter P

4.2 Examining Human Pedigrees  Determine trait has dominant or recessive inheritance pattern  Predict genetic risk for: Pregnancy outcome Adult-onset disorder In future offspring

Three Possible Patterns of Inheritance  Autosomal recessive  Autosomal dominant  X-linked recessive  Autosomal on chromosomes 1–22  X-linked traits on the X chromosome

Autosomal Recessive  Unaffected parents can have affected children  All children of affected parents are affected  Both parents Aa, risk of affected child is 25%  ~Equal affected male and female  Both parents must transmit the gene for a child to be affected

Autosomal Recessive Pedigree

Autosomal Recessive Genetic Disorders

Albinism  A = normal coloring; a = albinism  Group of genetic conditions, lack of pigmentation (melanin) in the skin, hair, and/or eyes  Normally, melanin in pigment granules inside melanocytes  In albinism, melanocytes present but cannot make melanin  Oculocutaneous albinism type I (OCA1)

Cystic Fibrosis (CF)  C = normal; c = cystic fibrosis  CF affects glands that produce mucus and digestive enzyme  CF causes production of thick mucus in lungs blocks airways  Develop obstructive lung diseases and infections  Identified CF gene and protein (CFTR)

Sickle Cell Anemia (SCA)  S = normal red blood cells; s = sickle  High frequency in areas of West Africa, Mediterranean Sea, India  Abnormal hemoglobin molecules aggregate to form rods  Red blood cells, crescent- or sickle-shaped, fragile and break open

Normal and Sickled Cells

Autosomal Dominant (1)  Requires one copy of the allele (Aa) rarely present in a homozygous condition (AA)  aa: Unaffected individuals  Affected individual has at least one affected parent  Aa X aa: Each child has 50% chance of being affected

Autosomal Dominant (2)  ~Equal numbers of affected males and females  Two affected individuals may have unaffected children  Generally, AA more severely affected, often die before birth or in childhood

Autosomal Dominant Pedigree

Autosomal Dominant Genetic Disorders

Animation: Chromosomes and Human Inheritance (autosomal-dominant inheritance)

Animation: Chromosomes and Human Inheritance (autosomal-recessive inheritance)

Neurofibromatosis (NF)  N = Neurofibromatosis 1; n = normal  Many different phenotypes  Café-au-lait spots, or noncancerous tumors in the nervous system can be large and press on nerves  Deformities of the face or other body parts (rarely)  NF gene has a very high mutation rate

Neurofibromatosis

Huntington Disease (HD)  H = Huntington disease; h = normal  Causes damage in brain from accumulation of huntingtin protein  Symptoms begin slowly (30–50 years old)  Affected individuals may have already had children (50% chance with one Hh parent)  Progressive neurological signs, no treatment, die within 10–25 years after symptoms

Adult-Onset Disorders  Expressed later in life  Present problems in pedigree analysis, genetic testing may be required  Examples: Huntington disease (HD) Adult polycystic kidney disease (ADPKD)  Both examples are autosomal dominant

4.3 X-Linked Recessive Traits  Genes on X chromosome: X-linked  Genes on Y chromosome: Y-linked  For X-linked traits: Females XX, XX*, or X*X* Males XY or X*Y Males cannot be homozygous or heterozygous, they are hemizygous for genes on X Distinctive pattern of inheritance

X-Linked Recessive Inheritance  Mother gives one X chromosome to offspring  Father gives X to daughters and Y to sons  Sons carry X from mother  For recessive traits, X*X* and X*Y affected  More males affected

Pedigrees: X-Linked Inheritance

X-Linked Recessive Genetic Disorders

Inheritance of X-Linked Disorder

Animation: Chromosomes and Human Inheritance (X-linked inheritance)

Duchenne Muscular Dystrophy (DMD) (1)  X M = normal; X m = muscular dystrophy  Most common form, affects ~1/3,500 males  Infants appear healthy, symptoms age ~1–6 years  Rapid, progressive muscle weakness  Usually must use a wheelchair by age 12  Death, age ~20 from respiratory infection or cardiac failure

Duchenne Muscular Dystrophy (DMD) (2)  DMD gene on the end of X chromosome  Encodes protein dystrophin that supports plasma membrane during contraction  If dystrophin absent or defective, cells are torn apart  Two forms: DMD, and less-serious Becker muscular dystrophy (BMD)

Cells of a Person with MD

Hemophilia  X H = normal; X h = hemophilia  Lack of clotting: factor VIII in blood  Affected individuals hemorrhage, often require hospitalization to treat bleeding  Hemophilia A most common form of X-linked hemophilia  Females affected if X h X h, both parents must carry the trait

Factor VIII  1980s, half of all people with hemophilia became infected with HIV  Recombinant DNA technology now used to make clotting factors free from contamination