Download sex-linked genes

GENETIC HISTORY
• 1860’S: MENDEL’S LAWS OF
SEGREGATION AND ASSORTMENT
• 1875: CYTOLOGISTS WORKED OUT
PROCESS OF MITOSIS
• 1890: MEIOSIS FIGURED OUT
• 1900: THREE BOTANISTS REDISCOVERED
MENDEL’S LAWS
• 1902: MENDEL’S LAWS AND MEIOSIS
WERE STUDIED AND IDEAS CONVERGED
CHROMOSOME THEORY OF
INHERITANCE
• ACCORDING TO THIS THEORY
(DERIVED FROM THE WORK STATED)
• 1) MENDELIAN FACTORS OR GENES
ARE LOCATED ON CHROMOSOMES
• 2) IT IS THE CHROMOSOMES THAT
SEGREGATE AND INDEPENDENTLY
ASSORT
CHROMOSOMAL BASIS OF MENDEL’S LAWS
EARLY 1900’S
THOMAS MORGAN
• MORGAN USED FRUIT FLIES TO STUDY
CHROMOSOMES: THEY ONLY HAVE 4
PAIRS WHICH ARE EASILY SEEN WITH
MICROSCOPE
• MORGAN TRACED A GENE TO A SPECIFIC
CHROMOSOME
• THIS PROVIDED CONVINCING EVIDENCE
THAT MENDEL’S INHERITABLE FACTORS
ARE LOCATED ON CHROMOSOMES
DISCOVERY OF A SEX LINKAGE
• MORGAN DEDUCED THAT EYE COLOR IS
LINKED TO SEX AND THAT THE GENE FOR
EYE COLOR IS LOCATED ONLY ON THE X
CHROMOSOME.
• WILD TYPE = NORMAL PHENOTYPE
• MUTANT = ALTERNATIVE TO NORMAL
• SEX-LINKED GENES = GENES LOCATED ON
SEX CHROMOSOMES. THE TERM IS MOSTLY
APPLIED ONLY TO GENES ON THE X
CHROMOSOME
SEX-LINKED INHERITANCE
LINKED GENES
• GENES THAT ARE LOCATED ON THE SAME
CHROMOSOME AND THAT TEND TO BE
INHERITED TOGETHER
• LINKED GENES DO NOT ASSORT
INDEPENDENTLY
• A DIHYBRID CROSS FOLLOWING TWO
LINKED GENES WILL NOT PRODUCE AN F2
PHENOTYPIC RATIO OF 9:3:3:1
LINKED GENES
MORGAN PROPOSED THAT THESE RATIOS WERE DUE TO
LINKAGE. THE GENES FOR BODY COLOR AND WING SIZE
ARE ON THE SAME CHROMOSOME AND ARE USUALLY
INHERITED TOGETHER
LINKED GENES
MORGAN PROPOSED THAT THESE RATIOS WERE DUE TO
LINKAGE. THE GENES FOR BODY COLOR AND WING SIZE
ARE ON THE SAME CHROMOSOME AND ARE USUALLY
INHERITED TOGETHER
GENETIC RECOMBINATION
• THE PRODUCTION OF OFFSPRING WITH
NEW COMBINATIONS OF TRAITS
DIFFERENT FROM THOSE COMBOS
FOUND IN THE PARENTS; RESULTS FROM
THE EVENTS OF MEIOSIS AND RANDOM
FERTILIZATION
• PARENTAL TYPES= OFFSPRING THAT
HAVE THE SAME PHENOTYPE AS ONE
PARENT
• RECOMBINANTS = OFFSPRING WHOSE
PHENOTYPES DIFFER FROM EITHER
PARENT
CROSSING OVER:
RECOMBINATION OF LINKED
GENES
• IF GENES ARE TOTALLY LINKED, SOME POSSIBLE
PHENOTYPIC COMBOS SHOULD NOT APPEAR; BUT
SOMETIMES THE UNEXPECTED PHENOTYPES DO
APPEAR
• MORGAN DID A STUDY AND FOUND THAT 17% OF
OFFSPRING WERE RECOMBINANTS, WHERE HE
THOUGHT THE GENES WERE LINKED
• CROSSING OVER ACCOUNTS FOR THIS
RECOMBINATION (NOT KNOWN THEN)
RECOMBINATION DUE TO CROSSING OVER
RECOMBINATION DATA
• SCIENTISTS USED RECOMBINATION
FREQUENCIES BETWEEN GENES TO MAP
THE SEQUENCE OF LINKED GENES ON A
PARTICULAR CHROMOSOME
• MORGAN’S DROSOPHILA STUDIES SHOWED
THAT SOME GENES ARE LINKED MORE
TIGHTLY THAN OTHERS
• EX: THE RECOMBINATION FREQUENCY
BETWEEN THE b and vg LOCI IS ABOUT 17%
GENETIC LOCI
• ONE OF MORGAN’S STUDENTS THEORIZED
THAT THE PROBABILITY OF CROSSING OVER
BETWEEN TWO GENES IS DIRECTLY
PROPORTIONAL TO THE DISTANCE BETWEEN
THEM
• RECOMBINATION FREQUENCIES BETWEEN
GENES WERE USED TO ASSIGN THEM A LINEAR
POSITION ON A CHROMOSOME MAP
• IF LINKED GENES ARE SO FAR APART THAT THE
RECOMBO FREQ. IS 50%, THEN THEY ARE NO
DIFFERENT FROM UNLINKED GENES THAT
ASSORT INDEPENDENTLY
RECOMBINATION FREQUENCIES
ONE MAP UNIT = 1% RECOMBINATION FREQUENCY, SO 17%
WILL EQUAL APPROX 17 MAP UNITS
A PARTIAL GENETIC MAP OF DROSOPHILA
SEX CHROMOSOMES
• IN MOST SPECIES, SEX IS DETERMINED
BY THE PRESENCE OR ABSENCE OF
SPECIAL CHROMOSOMES
• HETEROGAMETIC SEX = THE SEX THAT
PRODUCES TWO KINDS OF GAMETES AND
DETERMINES THE SEX OF THE OFFSPRING
• HOMOGAMETIC SEX = THE SEX THAT
PRODUCES ONE KIND OF GAMETE
DIFFERENT CHROMOSOMAL SYSTEMS OF GENDER
SEX DETERMINATION IN
HUMANS
• MALES ARE HETEROGAMETIC (XY)
• FEMALES ARE HOMOGAMETIC (XX)
• WHETER AN EMBRYO DEVELOPS INTO A
MALE OF FEMALE DEPENDS UPON THE
PRESENCE OF THE Y CHROMOSOME
• SRY GENE: SEX DETERMINING REGION
ON Y CHROMOSOME THAT TRIGGERS
EVENTS THAT LEAD TO TESTE
DEVELOPMENT; IN ABSENCE OF SRY, THE
GONADS DEVELOP INTO OVARIES
SEX-LINKED DISORDERS
• SEX-LINKED TRAITS USUALLY REFERS
TO X-LINKED TRAITS
• THE X CHROMOSOME IS MUCH LARGER
THAN THE Y, GIVING MORE X-LINKED
TRAITS
• MOST X-LINKED GENES HAVE NO
HOMOLOGOUS LOCI ON THE Y
CHROMOSOME
• MOST GENES ON THE Y NOT ONLY HAVE
NO X COUNTERPARTS, BUT THEY
ENCODE FOR STRICTLY MALE TRAITS
(EX: TESTIS)
SEX-LINKED DISORDERS
• FATHERS PASS X-LINKED ALLELES TO ALL
THEIR DAUGHTERS ONLY
• MALES RECEIVE THEIR X CHROMOSOME
ONLY FROM THEIR MOTHERS
• FATHERS CANNOT PASS SEX-LINKED TRAITS
TO THEIR SONS
SEX-LINKED DISORDERS
• MOTHERS CAN PASS SEX-LINKED ALLELES
TO BOTH SONS AND DAUGHTERS
• FEMALES RECEIVE TWO X
CHROMOSOMES, ONE FROM EACH PARENT
• MOTHERS PASS ON ONE X CHROMOSOME
TO EVERY DAUGHTER AND SON
SEX-LINKED RECESSIVE
• A FEMALE WILL EXPRESS TRAIT ONLY
IF SHE IS HOMOZYGOUS
• MORE MALES HAVE SEX-LINKED
DISORDERS, AS THEY ONLY HAVE ONE
X CHROMOSOME; FEMALES CAN BE A
HETERZYGOUS CARRIER, BUT NOT
SHOW THE TRAIT HERSELF
• A CARRIER THAT MATES WITH NORMAL
MALE WILL PASS THE TRAIT ON TO
HALF HER SONS AND DAUGHTERS
SEX-LINKED RECESSIVE TRAITS
X-INACTIVATION IN
FEMALE MAMMALS
• IN FEMALE MAMMALS, MOST DIPLOID
CELLS HAVE ONLY ONE FULL FUNCTIONAL
X CHROMOSOME
• EACH EMBRYONIC CELL INACTIVATES ONE
OF THE TWO X CHROMOSOMES
• THE INACTIVE X CHROMOSOME
CONTRACTS INTO A DENSE OBJECT
CALLED A BARR BODY
BARR BODY
• MOST BARR BODY GENES ARE NOT
EXPRESSED
• THEY ARE REACTIVATED IN
GONADAL CELLS THAT UNDERGO
MEIOSIS TO FORM GAMETES
FEMALE MAMMALIAN
CELLS
• FEMALE MAMMALS ARE A MOSAIC OF TWO
TYPE OF CELLS: THOSE WITH AN ACTIVE
MATERNAL X AND THOSE WITH AN ACTIVE
PATERNAL X
• WHICH OF THE TWO X’S WILL BE INACTIVATED
IS DETERMINED RANDOMLY IN EMBRYONIC
CELLS
• AFTER AN X IS INACTIVATED, ALL MITOTIC
DECENDNTS WILL HAVE THE SAME INACTIVE X
• IF A FEMALE IS HETEROZYGOUS FOR A SEXLINKED TRAIT, ABOUT HALF OF HER CELLS
WILL EXPRESS ONE ALLELE AND THE OTHER
CELLS WILL EXPRESS THE ALTERNATE
CHROMOSOMAL ERRORS
AND EXCEPTIONS
• MEIOTIC ERRORS AND MUTAGENS
CAN CAUSE MAJOR CHROMOSOMAL
CHANGES SUCH AS ALTERED
CHROMOSOME NUMBERS OR
ALTERED CHROMOSOMAL
STRUCTURE
NONDISJUNCTION
• MEIOTIC OR MITOTIC ERROR DURING
WHICH CERTAIN HOMOLOGOUS
CHROMOSOMES OR SISTER CHROMATIDS
FAIL TO SEPARATE
• THERE ARE 2 MAIN TYPES OF
NONDISJUNCTION: ANEUPLOIDY AND
POLYPLOIDY
MEIOTIC NONDISJUNCTION
ANEUPLOIDY
• HAVING AN ABNORMAL NUMBER OF
CERTAIN CHROMOSOMES
• WHEN AN ANEUPLOID ZYGOTE DIVIDES BY
MITOSIS, IT TRANSMITS THE PROBLEM TO
ALL EMBRYONIC CELLS
• TRISOMIC = AN ANEUPLOID CELL THAT HAS A
CHROMOSOME IN TRIPLICATE (DOWN’S
SYNDROME)
• MONOSOMIC- A CELL MISSING A
CHROMOSOME
POLYPLOIDY
• A CHROMOSOME NUMBER THAT IS MORE THAN
TWO COMPLETE CHROMOSOME SETS
• IS COMMON IN PLANTS AND IMPORTANT IN
PLANT EVOLUTION
• TRIPLOIDY = THREE HAPLOID CHROMOSOME
SETS (3N);MAY BE PRODUCED BY FERTILIZATION
OF ABNORMAL DIPLOID EGG PRODUCED BY
NONDISJUNCTION OF ALL CHROMOSOMES
• TETRAPLOIDY = FOUR HAPLOID CHROMOSOME
SETS (4N);MAY RESULT IF A DIPLOID ZYGOTE
UNDERGOES MITOSIS WITHOUT CYTOKINESIS.
SUBSEQUENT NORMAL MITOSIS WOULD PRODUCE
A 4N EMBRYO
ALTERATIONS OF
CHROMOSOMES
• CHROMOSOME BREAKAGE CAN ALTER
THEIR STRUCTURE IN FOUR WAYS:
• 1) DELETION = CHROMOSOMES LOSE A
FRAGMENT LACKING A CENTROMERE
• 2) DUPLICATION = FRAGMENTS MAY JOIN TO A
HOMOLOGOUS CHROMOSOME
• 3) TRANSLOCATION = FRAGMENTS MAY JOIN
TO A NONHOMOLOGOUS CHROMO.
• 4) INVERSION = FRAGMENTS MAY REATTACH
TO THE ORIGINAL CHROMO. IN REVERSE
ORDER
ALTERATIONS OF
CHROMOSOMES
POSITION EFFECT - INFLUENCE ON A GENE’S EXPRESSION
BECAUSE OF ITS LOCATION AMONG NEIGHBOR GENES
HUMAN DISORDERS DUE TO
CHROMOSOMAL ALTERATIONS
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DOWN’S SYNDROME - TRISOMY 21
PATAU SYNDROME - TRISOMY 13
EDWARD’S SYNDROME - TRISOMY 18
KLEINFELTER SYNDROME - USUALLY XXY,
BUT ALSO XXYY, XXXY, XXXXY
TRIPLE X SYNDROME - XXX
TURNER SYNDROME = XO
CRI DU CHAT - DELETION ON #5
CHRONIC MYELOGENOUS LEUKEMIA
(CML)-TRANSLOCATION ON #22 WITH SMALL
FRAGMENT ON #9
GENOMIC IMPRINTING
• CAUSES CERTAIN GENES TO BE
DIFFERENTLY EXPRESSED IN THE
OFFSPRING DEPENDING UPON WHETHER
THE ALLELES WERE INHERITED FROM THE
OVUM OR THE SPERM
• PRADER-WILLI SYNDROME AND ANGELMAN
SYDROME-SAME DELETION ON #15;
SYMPTOMS DIFFER DEPENDING ON WHICH
PARENT GAVE THE GENE
• FRAGILE-X SYNDROME - AN ABNORMAL X
CHROMOSOME, THE TIP HANGS ON THE REST
OF THE CHROMOSOME BY A THIN DNA
THREAD; MOST COMMON GENETIC CAUSE OF
MENTAL RETARDATION; MORE LIKELY TO
APPEAR IF X IS INHERITED FROM MOTHER
GENOMIC IMPRINTING
NOTICE, THE
IMPRINTS ARE
NOT PASSED
FROM
GENERATION
TO GENERATION