Pedigrees, karyotypes, and genetic disorders CLE 3210.4.4 Compare different modes of inheritance: sex linkage, co-dominance, incomplete dominance, multiple alleles, and polygenic traits. CLE 3210.4.6 Describe the connection between mutations and human genetic disorders.

Overview Review karyotypes and chromosome type Discuss mutations and various genetic disorders Compare these with sex-linked inheritance Apply the use of karyotypes and pedigrees to better understand inheritance

Karyotypes A karyotype is an organized profile of an individual’s chromosomes. In a karyotype, chromosomes are arranged and numbered by size, from largest to smallest. Humans have 46 chromosomes or 23 pairs. 22 of these pairs are autosomes. 1 pair are sex chromosomes, X and Y. Which chromsomes do females have? Males?

Normal Karyotype Autosomes (44)   Sex chromosomes (2)

*3 Chromosomes instead of 2 Abnormal Karyotype Autosomes (44)   Sex chromosomes (2) *3 Chromosomes instead of 2

KINDS OF MUTATIONS Mutations that produce changes in a single gene = Images from: http://www.bbc.co.uk/scotland/education/bitesize/higher/img/biology/genetics_adaptation/mutations/02gene_mutation.gif KINDS OF MUTATIONS Mutations that produce changes in a single gene = _________________ in whole chromosomes = _____________________ GENE MUTATIONS CHROMOSOMAL MUTATIONS

KINDS OF MUTATIONS BODY SOMATIC ________ CELLS = ___________ CELLS Somatic cell mutations can: ______________________ ______________________ _____________ Cause cancer Make cell not able to function Kill cell BUT _________ passed on to offspring WON’T BE

Kinds of Mutations ___________ = _________cells (sperm & eggs) GAMETES GERM Germ cell mutations ________ passed on to offspring CAN BE http://anthro.palomar.edu/biobasis/images/meiosis.gif

Many genetic ___________ result from MANY HUMAN GENES HAVE BECOME KNOWN THROUGH THE STUDY OF GENETIC DISORDERS Many genetic ___________ result from changes in the DNA code so _________________ proteins are produced. DISORDERS NON-FUNCTIONING http://patentdocs.typepad.com/photos/uncategorized/2007/05/28/dna1.gif

What do I need to know about each disorder? Which specific type of disorder it is: Autosomal Recessive Autosomal Dominant Sex-Linked Nondisjunction Codominant What causes it Characteristics of it

Autosomal Recessive Disorders Example: Albinism: AA = no albinism Aa = carrier for albinism aa = albino A mutation that creates a disfunctional protein that appears RECESSIVE to the working allele. Includes: Albinism Cystic Fibrosis Phenylketonuria (PKU) Tay-Sach’s disease Sickle-cell disease

Autosomal Recessive Disorders Albinism Characterized by lack of pigment in the skin, hair, and eyes.

Albinism

Autosomal recessive: CYSTIC FIBROSIS CAUSE: Loss of 3 DNA bases in a gene for the _____________ that transports _________ so salt balance is upset Causes a build up of _________________ in lungs and digestive organs . protein Cl- ions thick mucous Image from: BIOLOGY by Miller and Levine; Prentice Hall Publishing ©2006

Phenylketonuria (PKU) CAUSE: Mutation in gene for an ___________ that __________ an ___________ called phenylalanine Build up causes ________________________ ENZYME breaks down amino acid X X MENTAL RETARDATION http://biology.clc.uc.edu/courses/bio104/protein.htm

Phenylketonuria (PKU) ALL tested ____ babies are ________ for PKU before they leave the hospital. Treatment: Need a diet _____________________ to extend life and ______________ mental retardation If phenylalanine is an _____________, what type of foods should PKU patients avoid? __________________ LOW in phenylalanine PREVENT amino acid PROTEINS !

TAY-SACHS DISEASE ___________________ AUTOSOMAL RECESSIVE CAUSE: Mutation in gene for an ___________ that breaks down a kind of _________in the developing _________ Build up of lipids in brain cells leads to: mental retardation, blindness, and DEATH in early childhood ENZYME LIPID BRAIN Found more frequently in people with _______ _____________ ______________, ancestry Jewish Mediterranean Middle Eastern Image from: http://www.djsfoundation.org/images/Steeler%20pics%20Dylan.jpg

Tay-Sachs

CARRIER heterozygous A __________ person who carries a _________ allele for a genetic disorder, but ______________ the disorder themselves is called a _____________ heterozygous recessive doesn’t show CARRIER http://www.biochem.arizona.edu/classes/bioc460/spring/rlm/RLM36.1.html

A male who is a heterozygous carrier for an autosomal recessive disease marries a homozygous unaffected female. What is the chance of having an affected child? A child who is a carrier? 50 %; 50% 0%; 50% 50%; 0% 25%; 50%

DOMINANT AUTOSOMAL DOMINANT Huntington’s disease Achondroplasia A mutation that codes for a new protein whose action masks the normal allele appears as a ______________ mutation. Examples of _________________________ GENETIC DISORDERS: ____________________ DOMINANT AUTOSOMAL DOMINANT Huntington’s disease Achondroplasia

HUNTINGTON’S DISEASE ______________________ AUTOSOMAL DOMINANT CAUSE: Extra 40-100 ______________ at end of gene on chromosome 4 The _____________ . . . the more __________ the symptoms. CAG repeats more repeats severe http://www.healthsystem.virginia.edu/internet/huntdisease/images/cag.gif

HUNTINGTON’S DISEASE loss Huntington’s brain loss Causes progressive _____ of ________________ and ___________function muscle control mental 1 in 10,000 people in U.S. have Huntington’s disease http://www.scielo.br/img/revistas/bjmbr/v39n8/html/6233i01.htm Normal brain

A person with Huntington’s disease has a _____ chance of passing the disorder on to their offspring. 50% Problem: Symptoms of disorder usually don’t show until ____________ . . . so you don’t know you have it until ________ you have had children. MIDDLE AGE AFTER

ACHONDROPLASIA (One kind of Dwarfism) AUTOSOMAL DOMINANT CAUSE: ___________________________ gene 1 in 20,000 births Mother has achondroplasia Father has diastrophic displasia, a recessive disorder 200,000 “little people” worldwide

Autosomal Dominant Disorders Achondroplasia 99.96% of all the people in the world are homozygous recessive for this trait (aa). Interesting fact: The AA (homozygous dominant) genotype of this trait is lethal and will result in a spontaneous abortion of the fetus. The only viable genotype is Aa.

Activity 1: With a partner Take 5 minutes and draw a two-circle Venn Diagram to compare and contrast: Autosomal recessive Vs. autosomal dominant

BY ____________________ DISORDERS CAUSED BY ____________________ ____________________ AUTOSOMAL CODOMINANT ALLELES SICKLE CELL DISEASE CAUSE: T changed to A in gene for __________________ (protein in red blood cells that carries oxygen in blood) HEMOGLOBIN

SICKLE CELL DISEASE SYMPTOMS: _____________ become sickle shaped in persons with ______ sickle cell ________ RED BLOOD CELLS TWO ALLELES

SICKLE CELL DISEASE Circulatory problems Cells stick in capillaries Loss of blood cells (anemia) Organ damage (brain, heart, spleen) Can lead to DEATH

SICKLE CELL DISEASE AFRICAN AMERICANS More common in _________________ 1 in 500 = have sickle cell disease 1 in 10 = carriers for allele Also affects persons of _______________ and _________________ descent Why do so many African Americans carry the sickle cell allele? MEDITERRANEAN MIDDLE EASTERN

SICKLE CELL DISEASE Many can trace their ancestry to west central Africa where ___________, a serious parasitic disease that infects red blood cells is common. MALARIA Images from: http://en.wikipedia.org/wiki/Malaria

HOMOZYGOUS sickle cell sickle disease HOMOZYGOUS malaria HETEROZYGOUS A person who is __________________ for the ____________allele (ss) will have _______________ A person who is _________________ for normal hemoglobin alleles will have normal blood cells, but can become infected with __________ (SS) A _________________ person (Ss) (with one normal/one sickle cell allele) is generally healthy and has the benefit of being _________ to malaria sickle cell sickle disease HOMOZYGOUS malaria HETEROZYGOUS resistant

Chromosomes that determine the sex of an organism = _________________ All other chromosomes = _________________ http://www.angelbabygifts.com/ Sex chromosomes autosomes Humans have two sex chromosomes and _____ autosomes X y 44

SEX DETERMINATION XX = female Xy = male

Who decides? X X Mom can give X X Dad can give X or y y X X X X X y SO ____ determines sex of the baby. If dad gives X with mom’s X = girl If dad give y with mom’s X = boy

Sex linked genes In addition to their role in determining sex of an organism, X and Y chromosomes have many other genes that are unrelated to sex. A gene on either sex chromosome is call a sex-linked gene. Congenital generalized hypertrichosis (CGH), the type that Danny Gomez has, is X-linked dominant; the gene that is mutated is found on the X chromosome. Sex-linked mutations can be either dominant or recessive. X-linked inheritance pattern from a heterozygote mother and unaffected father

PEDIGREES _______________are diagrams that show how are ____________ on __________ over several generations genes are passed in families

Drawing a pedigree chart

http://www.beavton.k12.or.us/sunset/academics/genetics.htm

Genes carried on X or Y chromsomes= ___________________ SEX LINKED TRAITS These traits show up in different _______________ in males and females because they move with the sex chromosomes percentages

EXAMPLE: Hairy pinna Y linked in males Y-LINKED GENES: Genes ______________ chromosome carried on Y EXAMPLE: Hairy pinna ONLY Y linked in males _________genes _____ show up _______

are carried on the X chromosome X-LINKED ____________ GENES: are carried on the X chromosome X-linked recessive disorders show up _____________ in ______ than females because males only have ______ X chromosome. MORE frequently MALES ONE

Or Males ONLY HAVE ONE X They either have the They are disorder normal DEFECTIVE NORMAL They either have the disorder They are normal Or

Females have one normal gene that works. FEMALES HAVE TWO X CHROMOSOMES DEFECTIVE NORMAL DEFECTIVE Females have one normal gene that works. Females __________ defective recessive alleles to show the disorder need 2

X-LINKED RECESSIVE Examples of ________________________ DISORDERS: ____________________ HEMOPHILIA COLORBLINDNESS DUCHENNE MUSCULAR DYSTROPHY

HEMOPHILIA Blood clotting proteins on X bleed to death CAUSE: Mutation in genes for __________________ carried ______ chromosome Blood clotting proteins are missing so person with this disorder can’t stop bleeding when injured; can ________________ from minor cuts or suffer internal bleeding from bruises or bumps. Blood clotting proteins on X bleed to death

COLORBLINDNESS Color vision Red-green CAUSE: Mutation in one of three genes for _______________ carried on X chromosome Persons with this disorder have trouble distinguishing colors. _________________ colorblindness is most common Seen in 1 in 10 males 1 in 100 females Color vision Red-green http://gizmodo.com/gadgets/peripherals/samsung-develops-lcd-for-colorblind-036306.php

Duchenne Muscular Dystrophy CAUSE: deletion in gene that codes for a _______________ Results in ____________________ and loss of ___________________ muscle protein progressive weakening skeletal muscle http://www.cadenhead.org/workbench/gems/jerry-lewis-telethon.jpg http://www.tokyo-med.ac.jp/genet/chm/dei.gif

________ traits show up _______ in _______ __________________ traits: What’s the pattern: ________ traits show up _______ in _______ __________________ traits: ______________________ than females. ________________ can be ________. _______________________ traits: BOTH ______ & _________ can be ________ Y-linked ONLY males X-linked recessive more common in males ONLY FEMALES carriers AUTOSOMAL RECESSIVE MALES FEMALES carriers

Activity 2 (group): Interpreting pedigrees Using your pedigree reference sheet, try to identify the inheritance pattern for each pedigree on the handout. Is it: Sex-linked dominant? Autosomal dominant? Autosomal recessive?

____________________________: Change in the ______________ or CHROMOSOMAL MUTATIONS ____________________________: Change in the ______________ or ____________ of chromosomes structure number

Homologous chromosomes ________________ during MEIOSIS = _________________________ One cell gets 2 copies of the chromosome the other cell gets none. fail to separate NONDISJUNCTION

Normal Meiosis Nondisjunction http://web.udl.es/usuaris/e4650869/docencia/gen_etica/meioferti2.html http://www.tokyo-med.ac.jp/genet/anm/domov.gif

Human Abnormalities caused by Non-Disjunction __________________ __________________ __________________ Down syndrome Klinefelter syndrome Turner syndrome

Down syndrome (= ____________) TRISOMY 21

Non-Disjunction Disorders Down Syndrome (1:700) Characterized by obvious physical features and mild to profound mental disabilities. Short stature, heart defects, short lifespan, often sexually underdeveloped and sterile. Caused by a duplication of the 21st chromosome (47 TOTAL) = TRISOMY 21.

Turner syndrome – “monosomy”

Non-Disjunction Disorders Turner’s Syndrome (1:5,000) THIS SYNDROME IS THE ONLY VIABLE MONOSOMY WHICH EXISTS IN HUMANS. 98% of these fetuses die prior to birth Individuals affected with this disorder develop as females only. Occurs when all or part of one of the X chromosomes is missing (45 TOTAL) =MONOSOMY X. Characterized by short stature, webbed neck, stocky build and absence of sexual development; normal intelligence.

Klinefelter syndrome XXy

Non-Disjunction Disorders Klinefelter’s Syndrome A condition which occurs in males only. Individuals with this disorder have an extra X sex chromosome (47 TOTAL) = TRISOMY XXY. This disorder can affect the stages of language, physical, and social development. Characteristics include small testes, breast enlargement and other feminine body attributes; normal intelligence.

Which disorder is this?

Which disorder is this?

Which disorder is this?

Polygenic traits – Eye color

Compare and contrast Complete dominance Incomplete dominance Co-dominance Sex-linked