Genetic Control of Growth & Maturation

1. Genetic Control of Growth & Maturation

2. Gregor Mendel (1822-1884) • Mendel studied the inherited traits of pea plants.

3. Gregor Mendel (1822-1884) • From his observations Mendel deduced that: • Each characteristic must be determined by a hereditary factor • There is a pair of hereditary factors; one from each parent

4. Gregor Mendel (1822-1884) • The law of uniformity: When two homozygotes with different alleles are crossed, all the offspring are identical and heterozygous. • The law of segregation: Each individual possesses two genes for a particular characteristic, only one of which can be transmitted. • The law of independent assortment: Members of different gene pairs segregate to offspring independently of one another.

5. Mendel’s Observations • Generation 1: • Yellow Round x Green Wrinkled • All Yellow Round offspring • Generation 2: • Yellow Round x Yellow Round • Generation 3: • Yellow Round, Yellow Wrinkled, Green Round. Green Wrinkled

6. Explanation of Mendel’s Observations • Generation 1: • Yellow Round (YYRR) x (Green Wrinkled (yyrr) • Generation 2: • Yellow Round (YyRr) x Yellow Round (YyRr) • Generation 3: • 9 Yellow Round (YYRR or YyRr) • 3 Yellow wrinkled (Yyrr or Yyrr) • 3 Green Round (yyRR or yyRr) • 1 Green Wrinkled (yyrr)

7. Pea Experiment • Click on the link below when you are connected to the internet • Pea Soup Website

8. Gene

9. Alleles • The two copies of each gene are called alleles, which may be identical (AA and aa) or different (Aa).

10. Homozygous • Refers to the state of carrying identical alleles at one or more gene loci (e.g. AABB or aabb).

11. Heterozygous • Refers to the state of carrying different alleles at one or more gene loci (e.g. AaBb).

12. Segregation of Alleles • Law of segregation is that alleles segregate, or separate, when the F1 generation produces gametes. • Alleles reside at specific loci, or sites, on the chromosomes within the DNA molecule. • A pair of homologous chromosomes contains two alleles at each locus and during gamete formation of meiosis, each gamete receives only one member of each homologous pair of chromosomes. Therefore, each gamete also receives only one allele of a particular locus.

13. CytogeneticsThe study of Chromosomes • 1903 Suttonand Boveriidependently proposed that the vehicle of hereditary factors or genes were the thread-like structures seen by light microscopy in the nucleus of each cell. • Chromosomes because of their affinity to take up certain stains (Greek: chroma, colour; soma, body). • Chromosomes are only being seen during the metaphase stage of cell division when they are maximally contracted. • Plant Chromosomes: von Nägeli in 1842. • Animal Chromosomes: Flemming (mitosis) 1882.

14. KaryotypeChromosome Complement of the Cell (1956) • Karyotyping is the process of imaging the chromosomes of the cell • 23 pairs of chromosomes • 44 autosomes + 2 sex chromosomes • 46, XX = Normal female • 46, XY = Normal male

15. Genotype • The genetic make up of the individual. • Typically, one refers to an individual's genotype with regard to a particular gene of interest • It refers to what combination of alleles the individual carries (either homozygous or heterozygous).

16. Phenotype • Any feature or characteristic of an organism or any group of characteristics (e.g. metabolism, physiology, or morphology). • The phenotype is the result of the interaction of the gene and environmental components.

17. Human Genome Project • The Human Genome Project (HGP) aimed to map and understand of all the genes of human beings. • In 1911, Alfred Sturtevant, then an undergraduate researcher in the laboratory of Thomas Hunt Morgan, realized that he could - and had to, in order to manage his data - map the locations of the fruit fly (Drosophila melanogaster) genes whose mutations the Morgan laboratory was tracking over generations. Sturtevant produced the very first gene map.

18. Human Genome Project • The hereditary material of all multi-cellular organisms is the famous double helix of deoxyribonucleic acid (DNA), which contains all of our genes. • DNA, in turn, is made up of four chemical bases, pairs of which form the "rungs" of the twisted, ladder-shaped DNA molecules. All genes are made up of stretches of these four bases, arranged in different ways and in different lengths.

19. Human Genome Project • By February 2003 HGP researchers fully mapped the the human genome. • determining the order, or "sequence," of all the bases in our genome's DNA; • making maps that show the locations of genes for major sections of all our chromosomes; • and producing what are called linkage maps, through which inherited traits (such as those for genetic disease) can be tracked over generations. • The HGP has revealed that there are probably somewhere between 30,000 and 40,000 human genes 50,000 genes to as many as 140,000). • National Human Genome Research Institute

20. Genetic Variation Program • Most of any one person's DNA, about 99.5 percent, is exactly the same as any unrelated person's DNA. Differences in the sequence of DNA among individuals are called genetic variation. • Genetic variation explains some of the differences among people, such as eye color and blood group. Genetic variation also plays a role in whether a person has a higher or lower risk for getting particular diseases. • Single gene differences in individuals account for some traits and diseases, such as the ABO blood group, cystic fibrosis and sickle cell disease.

21. Genetic Variation Program • More complex interrelationships among multiple genes and the environment are responsible for many common diseases, such as diabetes, cancer, stroke, Alzheimer's disease, Parkinson's disease, depression, alcoholism, heart disease, arthritis and asthma. • The Genetic Variation program supports research on genetic variation and how it relates to diseases, responses to drugs and environmental factors.

22. Genetic Expression • If all cells come from the one original zygote, how can the cells in the body vary so much • Some genes are permanently switched on • enzymes required for respiration etc • Some genes become switched off because they are no longer required to be functional in that particular cell or tissue. • Insulin is produced in pancreas cells, which must have the gene that codes for insulin switched on, and genes that are un-related to the role of the pancreas can be switched off. • Some other genes that will be functional during specialisation determine the physical characteristics of the cell, i.e. long and smooth for a muscle cell or indented like a goblet cell

23. Height • Polygenetic control

24. Parental Size • Average height of siblings approximates average height of parents • Parental stature adjusted growth curves • Birth size poorly correlated with adult size • Birth size correlated to mother’s size

25. Walton and Hammond (1938) Crossed large Shire horses with small Shetland ponies.

26. Walton and Hammond (1938) • Offspring of the crosses delivered to Shire dams were heavier than that of pure Shetland ponies, but below that of pure Shire offspring. • In contrast, the reciprocal cross-delivered to the Shetland dam was of the same weight at birth as the Shetland purebred foal. • The Shetland mother was able to down regulate the in utero growth of her foal sired by the much larger Shire horse, while the in utero environment provided by the larger Shire mother facilitated enhanced growth.

27. Allen et al. 2004 • Allen et al. (2004) • Confirmed the original observations of Walton & Hammond (1938) that a genetically large foal cannot reach its normal birthweight when gestated in a uterus that is smaller than normal, and the runting effect persists throughout life. • Furthermore, that genetically small foals will be born heavier than usual if gestated in the uteri of larger than normal mares and, similarly, this increased size persists to adulthood

28. 3 years of age 14 months of age Tb-in-P vs Tb-in-Tb Tb-in-P vs Tb-in-Tb P-in-Tb vs P-in-P P-in-P vs P-in-Tb

29. Allen et al. 2004 • Clear maternal size influence at birth • Lasting effect in postnatal development • Larger mother provided • Larger placental area • Greater microcotyledon density

30. Skin Colour • Skin colour depends on the degree of melanin found in skin cells. • There are two genes that control the production of melanin, each of which has a dominant and recessive expression. • 16 combinations of genotype when coding for skin colour, as seen below.

31. Skin Colour A person is born with one of five colours. External factors such as the UltraViolet light from the sun modify the genetic expression of colour.

32. Sex Linked Inheritance • A recessive trait on the X chromosome can find expression in a male

33. Sex Linked Inheritance Father’s contribution determines the sex of the child.

34. Hemophilia A • Mainly exhibited in males, due to recessive gene on X chromosome. • Only exhibited in double recessive females. • Sons of hemophiliac males will not have the gene • All daughters of male hemophiliacs will be carriers

35. Genetic DisordersChromosomal Disorders Numerical (Aneuploidy) due to nondisjunction. Structuralchromosomal due to a break in chromosome(s).

36. Genetic DisordersChromosomal Disorders • Numerical (Aneuploidy) due to nondisjunction • 1st or 2nd division of meiosis. An extra copy of a chromosome (trisomy) or a missing copy of a chromosome (monosomy). • Aneuploidy can also occur at mitosis after conception and leads to chromosomal mosaicism, a mixture of two or more cell lines each having a different number of chromosomes.

37. Genetic DisordersMendelian Disorders • Caused by a mutant allele or pair of mutant alleles at a single gene locus. • Either inherited or due to a new mutation. • Autosomal dominant or autosomal recessive. • Homo vs Heterozygous, Male vs Female? • Variable expressivity. • Penetrance • percentage of individuals exhibiting symptoms or signs • E.g. reduced penetrance in neurofibromatosis, a disorder characterized by multiple brown skin patches and benign growths.

38. Genetic DisordersMendelian Disorders • Autosomal recessive disorders only manifest in the homozygote. • Both sexes can be affected and heterozygotes (or carriers) are normal phenotypically. • Most individuals affected by an autosomal recessive disorder are born to healthy carrier parents. • 25% chance of homozygous normal • 50% chance of unaffected heterozygote carriers • 25% chance of having a homozygous affected offspring.. Cystic fibrosis is an autosomal recessive disorder progressive lung damage and poor growth

39. Genetic DisordersMendelian Disorders • Autosomal recessive disorders only manifest in the homozygote. • Both sexes can be affected and heterozygotes (or carriers) are normal phenotypically. • Most individuals affected by an autosomal recessive disorder are born to healthy carrier parents. • 25% chance of homozygous normal • 50% chance of unaffected heterozygote carriers • 25% chance of having a homozygous affected offspring.. Cystic fibrosis is an autosomal recessive disorder progressive lung damage and poor growth

40. Genetic DisordersMendelian Disorders • Autosomal recessive disorders only manifest in the homozygote. • Both sexes can be affected and heterozygotes (or carriers) are normal phenotypically. • Most individuals affected by an autosomal recessive disorder are born to healthy carrier parents. • 25% chance of homozygous normal • 50% chance of unaffected heterozygote carriers • 25% chance of having a homozygous affected offspring.. Cystic fibrosis is an autosomal recessive disorder progressive lung damage and poor growth

41. Genetic DisordersMultifactorial Disorders • Multifactorial disorders occur in more than one member of the family but do not follow a mendelian pattern of inheritance. • Interaction between environmental factors and a number of genes • Cleft lip, palate, spina bifida and common disorders in adults (e.g. diabetes mellitus, cancer, schizophrenia) are thought to be multifactorial in origin. • The risk for an individual of developing a multifactorial disorder is determined by the number of affected members in the family and the relationship to the patient.

42. Chromosome Aneuploidy • Aneuploidy = wrong number • Sex Chromosome Aneuploidies • Wrong complement of sex chromosomes • E.g. 47,XXX; 45,X0 • Autosomal Aneuploidies • Trisomy 21: Down Syndrome

43. 47, XXX • 1 : 960 • Normal in appearance • Usually fertile • 15-25% are mildly mentally retarded • Occurs due to nondisjunction in meiotic division of female

45. Turner’s Syndrome • 1 : 2,500 live female births (1:5,000 total live births). • There are indications that as few as 1:50 45, X0 conceptions are born alive. The others spontaneously abort. This suggests that the monosomy tends to be lethal.

46. Turner’s Syndrome • "Webbing" of the neck is often seen at birth and beyond. • The skin between the mastoid region and the shoulder expands before birth to cover a swollen jugular lymph sac. • The swelling usually goes down before birth, but the excess skin persists as a redundant fold. • A broad, shield-shaped chest and widely spaced nipples are also typical in this syndrome. • Short for their age; as adults they rarely exceed 5 feet in height.

47. Turner’s Syndrome • Ovarian dysgenesis and are infertile. • Cardiovascular abnormalities. • Many have a low posterior hairline. • Behind siblings in intellectual development. • Poor sexual development internally and externally.

48. 45, Y0 • Given that 45, X0 individuals exist, one might expect the viability of its male counterpart, 45, Y0. However, no such adults, children or embryos have been reported. • Indeed, Y0 or YY cells have never been observed. It has been suggested that these theoretically possible chromosome constitutions are incompatible with life, even with life as a very early embryo. Apparently there are genes necessary for life located on the X chromosome

49. Klinefelter Syndrome47, XXY • Incidence 1 : 1080

50. Klinefelter Syndrome47, XXY • Small testes, hyalinization of seminiferous tubules; aspermatogenesis • Often tall with disproportionately long limbs. • Intelligence is less than in normal siblings. • About 40% of these males have gynecomastia